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Clinical trial
Last Verified: June/30/2020
First Submitted: July/5/2020
First Posted: July/13/2020
Last Update Posted: July/20/2020
Sponsors: Institut du Cancer de Montpellier - Val d'Aurelle
Status: Not yet recruiting
Description

Many patients are modifying their diet after the diagnosis of cancer. There is a supposedly benefit, among the general public, of starving cancer cells with several diet deprivations.

Due to the lack of coherent scientific data, no evidence base recommendations can be made regarding the optimal diet during cancer and its effect on cancer growth.

The objective of this trial is to analyze the feasibility for patients with early luminal breast cancer to be compliant with a diet modification - ketogenic or proteins restricted diet - during 9 +/- 1 days, before breast cancer surgery.

The primary objective of the trial is to evaluate the compliance to the proposed diet.

The study will be conducted in patients with luminal early breast cancer, candidate to primary surgery, in order to study an homogeneous population of patients, with good performance status and without nutritional deprivation.

Metabolic changes on the main metabolic pathways and the potential antitumor effects related to these metabolic changes following the diet will be analyzed as secondary objectives of the study. We hope to find biological hypotheses to further test in a next larger prospective trial.

The impact of the patient's beliefs, anxiety and/or depression on the compliance will be analyzed as well.

Condition or disease
Condition or disease: Breast Cancer; Surgery
Location
France
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:Female
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: June/30/2020
First Submitted: June/8/2020
First Posted: July/14/2020
Last Update Posted: July/14/2020
Sponsors: University of Cologne
Status: Recruiting
Description

Recently, dietary models inducing ketosis have been shown to inhibit disease progression in animal models of PKD. Those beneficial dietary models included time-restricted feeding (TRF) without caloric reduction, ad libitum administered ketogenic diet (KD) and acute short-term fasting in mouse, rat and feline models of PKD.

In a PKD rat model, TRF without caloric reduction resulted in a strong inhibition of mTOR signaling, proliferation and fibrosis in the affected kidneys. The adminstration of an ad libitum fed KD led to similar results. In rat, mouse and feline models of PKD, acute fasting led to a significant reduction of cyst volume. Therefore, cystic cells seem to be metabolically inflexible and exhibit an altered metabolism characterized by increased glycolysis and, amongst others, defective fatty acid oxidation, similar to the Warburg effect in cancer. (Torres, Kruger et al. 2019)

While those beneficial observations were made in mouse, rat and feline models of PKD, the effects of a ketogenic diet in human ADPKD patients have not been investigated yet, even though the adminstration of ketogenic diets is used as a treatment for epilepsy in children since the 1920s and fasting is one of the oldest medical procedures.

Therefore, the aim of the present study is to investigate the effects of a short-period ketonic state in 10 ADPKD patients with fast progressive disease.

10 ADPKD-patients (aged 18-60 years, CKD G 1-3a) will be enrolled after giving informed consent. These 10 subjects will go through four trial-related visits. During these visits, physical examinations will be performed, blood will be drawn, urine will be collected and ketone body measurements in breath, blood and urine will be carried out. Each study visit includes an abdominal MRI-scan. Between visit 1 and visit 2, patients will eat their regular carbohydrate-rich diet. After visit 2, a ketonic state will be induced in those patients. Patients can choose whether the ketonic state will be induced by acute fasting for 72 hours (under sufficient water consumption and salt substitution) or by eating a KD for 14 days. Study visit 3 will take place within 72 hours after finishing the dietary intervention. After study visit 3, patients will restart eating their regular diet. Study visit 4 will provide follow-up data 3-6 weeks after the dietary intervention.

After study completion, the relative difference of TKV measured by MRI-based volumetry of the kidneys immediately before and immediately after the ketonic state, will be compared to TKV growth/decline while eating a regular carbohydrate-rich diet.

In general, patients are counselled in our outpatient department as part of "The German AD(H)PKD Registry" (more than 700 patients enrolled). As from those patients, clinical data, laboratory data and imaging studies are present, identification and recruitment of patients with fast rapidly progressing disease will be facilitated. Also, the investigators are closely liaised with the German self-help group PKDCure (PKD Familiaere Zystennieren e.V.), which is dedicated to ADPKD-linked research. This will facilitate recruitment of patients even more.

Data obtained from the study visits will be collected. The parameters listed below constitute the core data set, additional parameters can be included if considered essential.

Registered patients will be provided with diaries for the documentation of feeling of hunger, problems and discomforts as well as acetoacetate concentrations in breath. Patients are also provided with a portable breath-analyzer to measure acetoacetate concentrations in breath in between study visits. Study diaries are collected on Visit 4.

Data capture will be performed at each study visit after enrollment.

Condition or disease
Condition or disease: ADPKD
Location
Germany
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: May/31/2020
First Submitted: April/15/2020
First Posted: April/23/2020
Last Update Posted: June/16/2020
Sponsors: Johns Hopkins University
Status: Not yet recruiting
Description

Coronavirus disease (COVID-2019) is a devastating viral illness that originated in Wuhan China in late 2019. The number of confirmed cases worldwide has nearly reached 2 million and more than 125,000 people have died. Early studies from Wuhan reported a mortality rate of 2-3% with lower rates in surrounding provinces as the disease spread (closer to 0.7% of confirmed cases). One hypothesized cause for the higher mortality rate in Wuhan compared to surrounding regions was the rapid "surge" of COVID-19 infections before the disease was identified and social distancing implemented. Critically ill patients developed acute respiratory distress syndrome with inflammatory pulmonary edema and life-threatening hypoxemia requiring mechanical ventilation. This resulted in a significant strain on health-care resources such as availability of mechanical ventilators to treat patients with acute respiratory failure. As the disease spreads worldwide, strategies for reducing duration of ventilator support in patients with COVID-19 could significantly reduce morbidity and mortality of these individuals and future patients requiring this severely limited life-saving resource.

Alterations in macronutrient composition may be leveraged to improve ventilation and inflammation in COVID-19 patients. The ketogenic diet is a high fat, low carbohydrate, adequate protein diet that promotes ketone body production through hepatic metabolism of fatty acids. High fat, low carbohydrate diets have been shown to reduce duration of ventilator support and partial pressure carbon dioxide in patients with acute respiratory failure. Switching from glucose to fat oxidation lowers the respiratory quotient, thereby reducing the amount of carbon dioxide produced. This reduces ventilator demands and may improve oxygenation by lowering alveolar carbon dioxide levels, ultimately reducing time on mechanical ventilation. A study published in 1989 compared 10 participants intubated for acute respiratory failure and randomized to a high-fat, low carbohydrate diet and 10 participants receiving a standard isocaloric, isonitrogenous diet and showed a decrease in the partial pressure of carbon dioxide of 16% in the ketogenic diet group compared to a 4% increase in the standard diet group (p=0.003). The patients in the high-fat diet group had a mean of 62 fewer hours on a ventilator (p = 0.006) compared to the control group.

The high-fat diet used in the study had a ratio of 1.2:1 fat to protein and carbohydrate combined in grams. The ketogenic diet, which has been used safely and effectively in patients with chronic epilepsy for nearly one century and more recently in critically ill, intubated patients for the management of refractory and super-refractory status epilepticus has a 4:1 ratio (90% fat kilocalories). While a 1:1 ratio diet can produce a state of mild metabolic ketosis (typically ~ 1 mmol/L of the ketone body betahydroxybutyrate, measured in serum), a higher 4:1 ratio ketogenic diet can produce higher ketone body betahydroxybutyrate levels and more rapidly (up to 2 mmol/L within 24 hours of initiation). One study of obese patients treated with ketogenic diet reported that increases in ketone body production correlated with a lower partial pressure of carbon dioxide levels. A more recent study showed that patients with refractory epilepsy had a reduction in the respiratory quotient and increased fatty acid oxidation without a change in the respiratory energy expenditure with chronic use of the ketogenic diet. These findings were replicated in healthy subjects on ketogenic diet compared to a control group and patients on a ketogenic diet also had a significant reduction in carbon dioxide output and partial pressure of carbon dioxide. The authors concluded that a ketogenic diet may decrease carbon dioxide body stores and that use of a ketogenic diet may be beneficial for patients with respiratory failure. Even in patients without hypercapnia (primarily hypoxic respiratory failure), lowering carbon dioxide production permits lowering tidal volumes - a cornerstone of acute respiratory distress syndrome management.

In addition to reducing the partial pressure of carbon dioxide, metabolic ketosis reduces systemic inflammation. This mechanism could be leveraged to halt the cytokine storm characteristic of COVID-19 infection. Several studies provide evidence that pro-inflammatory cytokine production is significantly reduced in animals fed a ketogenic diet in a variety of disease models. In a rodent model of Parkinson's disease, mice were found to have significantly decreased levels of pro-inflammatory, macrophage secreted cytokines interleukin-1β, interleukin-6, and Tumor necrosis factor-alpha after 1 week of treatment with a ketogenic diet. Likewise, rats pretreated with a ketogenic diet prior to injection with lipopolysaccharide to induce fever did not experience an increase in body temperature or interleukin-1β, while significant increases were seen in control animals not pretreated with a ketogenic diet. In a mouse model of NLRP3-mediated diseases as well as human monocytes, the ketone body beta-hydroxybutyrate inhibited the NLRP3 inflammasome-mediated production of interleukin-1β and interleukin-18. These findings have been replicated in several recent animal studies and preliminary studies in humans. The hypothesis of this study is that through induction of metabolic ketosis combined with carbohydrate restriction, a ketogenic diet is protective against the cytokine storm in COVID-19. With its carbon dioxide-lowering and anti-inflammatory properties, a ketogenic diet may become an important component of the acute respiratory distress syndrome arsenal with immediate relevance to the current COVID-19 pandemic.

Condition or disease
Condition or disease: COVID-19
Location
-
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
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Clinical trial
Last Verified: March/31/2020
First Submitted: April/2/2020
First Posted: April/14/2020
Last Update Posted: April/14/2020
Sponsors: University of Primorska
Status: Recruiting
Description

Vegetarian and vegan diets have been shown to have health benefits on preventing cardiovascular diseases, type 2 diabetes and cancer. They are both gaining popularity in public. Ketogenic diet has also been very popular, especially due to its effect on weight loss and blood glucose parameters. To our knowledge there, are no studies that compare long-term effects of all three diets and omnivorous diets with regards to health parameters and gut microbiota composition.

The aim of the proposed study is to investigate the link between different diets and health parameters, such as parameters related to longevity, inflammation, stress and gut microbiota composition. The study is designed to compare different diets and their relationship with the body as a whole.

Condition or disease
Condition or disease: Healthy Diet; Microbiota
Location
Slovenia
Phase
-
Study design
Study type:Observational [Patient Registry]
Observational Model:Cohort
Time Perspective:Prospective
Eligibility Criteria
Ages Eligible for Study:20 Years to 20 Years
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: June/30/2020
First Submitted: March/22/2020
First Posted: July/7/2020
Last Update Posted: July/7/2020
Sponsors: Goethe University
Status: Recruiting
Abstract

Nutritional interventions such as ketogenic diet (KD) or fasting are currently under evaluation as anti-cancer treatment. In glioma patient cohorts, the feasibility and safety of fasting in addition to antitumor treatment has been shown. However, it is still unclear whether fasting exerts effects on the glioma tumor tissue at all, and whether fasting causes metabolic or immunological changes in the glioma microenvironment that could be exploited therapeutically. Therefore, the central contribution of this study is to characterize metabolic and immunological changes in the glioma tumor tissue induced by a fasting cycle of 72 hours prior to biopsy or resection.

Condition or disease
Condition or disease: Glioma, Mixed
Location
Germany
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: March/17/2020
First Posted: March/19/2020
Last Update Posted: March/30/2020
Sponsors: University Hospital, Angers
Status: Not yet recruiting
Description

This research study is a pilot study evaluating the tolerance of a ketogenic diet associated with a standard of care in patient with metastatic renal cell carcinoma.

The drugs involved in this study could be NIVOLUMAB + IPILIMUMAB, PEMBROLIZUMAB + AXITINIB, SUNITINIB or PAZOPANIB.

Cancer cells are known to have an increased glycolytic activity that allows them to product energy from anaerobic degradation of glucose. A ketogenic diet places the body in ketosis state. It forces the body to burn fat instead of glucose. Fat metabolism occurs via the mitochondrial oxidative phosphorylation. By reducing sugar intake and regulating energy metabolism, the ketogenic diet could contribute to limit tumor progression.

This diet will be introduced during one year, patient will be monitored closely with biological tests and radiological assessments every three month.

Condition or disease
Condition or disease: Metastatic Renal Cancer
Location
-
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: March/5/2020
First Posted: March/15/2020
Last Update Posted: March/16/2020
Sponsors: Jens Rikardt Andersen
Status: Not yet recruiting
Description

Abstract

At the Department of Highly Specialized Neurorehabilitation/Traumatic Brain Injury, Rigshospitalet (satellite department at Hvidovre Hospital), approximately 100 patients (pt.) are admitted with severe brain damage every year. From 2015 to 2017, 305 pt. were admitted. Out of the 305 pt., 162pt. (53%) had traumatic brain injury (TBI), 48pt. (16%) had apoplexy, 35pt. (12%) had other diagnoses (infections, tumors and almost drowning, etc.), 20pt. (7%) had spontaneous subarachnoid hemorrhage (SAH) and 24pt. (8%) had brain damage as a result of cardiac arrest.

TBI is a leading cause of injury-related morbidity and mortality worldwide. According to the Global Burden of Disease Study (2016), there were 27,08 million new cases of TBI globally in 2016. In Denmark, there were 17.302 new cases of TBI in 2016. Clinical studies have repeatedly shown major changes in cerebral energy metabolism after TBI. The secondary brain injury leads to metabolic cellular dysfunction, cerebral edema, and a complex injury cascade. The injury spread includes processes such as inflammation, edema, free radical damage, oxidative damage, ischemic injury, cerebral glucose metabolism disorder, and ion-mediated cell damage. Much of the neurological dysfunction that occurs in acute TBI also occurs in apoplexy, SAH and cerebral ischemia.

A very important adaptive metabolic response after brain injury is the utilization of alternative cerebral energy substrates, including lactate, but also ketone bodies (KB) such as β-hydroxybutyrate (BHB) and acetoacetate (AcAc). In addition to having a central role in the regulation of cerebral energy metabolism after brain injury, KB has other important neuroprotective properties, including attenuation of oxidative stress, apoptotic cell death, and microglial activation. Increasing KB metabolism through fasting or diet-induced ketosis promotes brain resistance to stress and injury, and attenuates acute cerebral injury. Therefore, supplementing with KB, e.g. through the use of a ketogenic diet (KD) with added medium chain fatty acids (MCT), has emerged as a potential non-pharmacological neuroprotective therapy.

KD has been used for many years for the treatment of refractory epilepsy in children and studies done on adults show promising results, but experience from several studies shows major compliance issues. KD has been shown to reduce cerebral edema and apoptosis, as well as improve cerebral metabolism and behavioral outcomes in TBI rodent models, but clinical human trials on adults with TBI are lacking. Apoplexy animal models show positive effects on pathological and functional outcomes of KD intervention or exogenous ketone administration. The only human trial of KD and apoplexy shows that KD is safe and tolerated by patients with acute apoplexy. Our hypothesis is that diet-induced ketosis will reduce the extent of secondary brain damage. The purpose of the trial is to investigate whether an intervention with a ketogenic diet supplemented with MCT is feasible for 8 weeks on hospitalized pt. with severe brain damage. This is the pre-study for a controlled study.

Condition or disease
Condition or disease: Brain Injuries; Traumatic Brain Injury; Subarachnoid Hemorrhage; Apoplexy; Anoxic Brain Injury; Neuroinfections
Location
Denmark
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:17 Years to 17 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: May/31/2020
First Submitted: December/29/2019
First Posted: January/17/2020
Last Update Posted: June/3/2020
Sponsors: Weill Medical College of Cornell University
Status: Recruiting
Description

This is a single-arm feasibility study to evaluate adherence to a ketogenic diet in patients with low tumor burden, treatment-naïve mantle cell lymphoma.

Subjects will be evaluated for eligibility and baseline assessments prior to initiating the ketogenic diet during the screening period and/or prior to initiating the ketogenic diet on Day 1. Eligible subjects will receive study treatment which will consist of a daily ketogenic diet for up to 12 weeks (Day 1 through Day 84). Subjects will be monitored with weekly assessments of adherence to diet and effects on serum metabolic markers, tumor specimens, and body composition.

After discontinuing the ketogenic diet, subjects will be followed for 28 days.

Condition or disease
Condition or disease: Mantle Cell Lymphoma; Ketogenic Dieting
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: August/31/2019
First Submitted: August/17/2019
First Posted: September/22/2019
Last Update Posted: September/30/2019
Sponsors: Maura Palmery
Status: Recruiting
Description

Young people are considered a population at risk of nutritional deficiencies due to bad eating habits, found especially among university students. In fact, the latter tend to change their eating habits when they begin their university studies, with adherence to a typically western diet that includes low consumption of fish, fruit and vegetables, monounsaturated and polyunsaturated fatty acids, and an increase in consumption of sugars, alcohol and "fast food", with the consequent increase in this population class of the risk of malnutrition and/or obesity, metabolic and cardiovascular diseases. These changes are due to the lack of experience in meal planning, with a consequent increase in the frequency of meals away from home, to the increase in the number of snacks or meals skipped to respect the timetable of the lessons, to the easier access to the fast food and limited economic resources. Among the unhealthy behaviors adopted by the students, in addition to the wrong eating habits, there are also reduced physical activity, increased sedentariness, alcohol consumption and smoking.

Over the past 20 years there has been an increase in obesity rates among university students who, especially for medical students, are closely related to specific habits such as: skipping breakfast, attending fast food, low fruit and vegetables consumption, and easy access to unhealthy foods from the machines. Among the freshmen, especially those who live far from families and find themselves independent for the first time in their lives, higher rates of weight gain and higher levels of stress have been reported, responsible for changes in food choices. In fact, to control stress levels, individuals are encouraged to prefer foods that are high in fat. Therefore, university students should be seen as a group that requires special attention regarding health promotion, especially food.

However, the interest in a healthy diet can lead to a psychological obsession known as orthorexia (ortho = just, oreksis = appetite), which consists in the persistent concern of maintaining the self-imposed diet to improve one's health. Nutritionists/dieticians and students are the categories of population most affected by orthorexia, with a prevalence in Italian nutrition science students of 35.9%. The typical behaviors of orthorexia can be associated with a negative image of one's own body, despite the subject's strong interest in appropriate and healthy food choices. However, as a result of extreme restriction/concern over one's diet, orthorhexics would tend to eliminate whole groups of foods with consequent nutritional deficiencies, malnutrition and weight loss. Furthermore, the typical eating behavior of orthoressia is associated with intense physical activity, suggesting that students who practice sports have a greater tendency to develop this disorder.

The high levels of stress recorded in university students were also related to the use of smart drugs and "smart nutrients", which university students, especially those in medicine (74.7%), use to enhance their cognitive abilities. The phenomenon of self-medication is one of the main problems for public health, with only 48% of the population of the European Union using prescribed drugs. Among the students of health professions high levels of self-medication with antibiotics are recorded in the absence of indication. Another trend that is of particular concern is the increase in the use of antidepressants among young people, which many of them take after disappointments in academic performance and which have negative side effects such as weight gain , altered lipid profile and risk of diabetes. Another category of substances that young people abuse or otherwise misuse are amphetamines, and the co-intake of stimulants, alcohol or other drugs is also of concern. Indeed, a recent study carried out on Italian and Spanish pharmacy students showed that Spaniards have a high percentage of drug use and that 38.4% of subjects take them in conjunction with alcohol; instead, Italian students have revealed that they rarely turn to the pharmacist and rely more on the advice of family or friends.

The university years therefore represent a period marked not only by food problems but also by stress, anxiety, depression and other psychological problems. However, it emerged that a high adherence to the Mediterranean diet would bring benefits at the cognitive level, with an improvement in the states of depression and anxiety and a better academic result. In addition to a healthy diet, even moderate and regular physical activity (90 minutes a week) has been shown to reduce levels of anxiety and depression with improved well-being and self-esteem. For this reason it is essential to promote this lifestyle among university students.

Different types of diet and bioactive compounds taken with the diet can also have an impact on the composition of the intestinal microbiota. In particular, the Mediterranean diet has been associated with a greater abundance of Bacteroidetes, Prevotellacea and Prevotella and a lower concentration of Firmicutes and Lachnospiraceae. Although several studies have investigated the eating habits of Spanish university students, only Scuri et al. investigated the use of drugs in Italian and Spanish university students, but limited the study to a well-defined sample represented by students of the only pharmacy faculty, because they were considered particularly careful and involved on this topic. It would therefore be interesting to evaluate this behaviour, including the tendency to self-medication, between Italian and Spanish students, including biomedical and not just pharmaceutical faculties, in order to have an overview of the behaviour of university students who support scientific studies, that should lead them to acquire more awareness of health problems, including the correct use of drugs. Furthermore, although several studies have investigated the effect of the Mediterranean diet on intestinal microbiota, little attention has been paid to the effect of this diet on the oral microbiota, despite the oral cavity being one of the most relevant microbial habitats from a clinical point of view, and it has been shown to be a significant risk factor for cardiovascular diseases, diabetes mellitus, bacteraemia and tumors. It is therefore interesting to analyse and investigate these aspects.

The aim of this study is to evaluate self-medication, adherence to the Mediterranean diet, the relationship between lifestyle and biomarkers of the metabolic and immunological status, and impact of eating habits on the oral microbiota composition.

Primary goals:

- Compare the prescription of drugs and the use of alcohol, energy drinks, supplements, dietary products and/or other types of nutraceuticals in Italian and Spanish university students.

- Compare the adherence to the Mediterranean diet in Italian and Spanish university students.

- Compare cardiovascular risk factors (obesity, hypertension, hyperglycemia, dyslipidemia and smoking habits) and ketosis in Italian and Spanish university students.

Secondary goals:

- Compare and evaluate the level of physical activity and the percentage of subjects with orthorexia nervosa in Italian and Spanish university students.

- Compare the frequency and type of meals consumed outside home, the type and consumption of food/beverages and adherence to special dietary regimes (vegetarian diet, ketogenic etc), in Italian and Spanish university students.

- Register other characteristics of interest (pathologies, anxiety/depressive symptoms, food neophobia, eating disorders, vaccinations and opinion on vaccines).

- Compare eating habits, salivary microbiota and salivary immunoglobulin A (IgA), interleukin-6 (IL-6) and cortisol levels in a sub-group of non-smoking Italian and Spanish students.

In the recruitment phase it will be sent to the subjects by e-mail:

- "The" INFORMATION NOTE AND CONSENT "

- "Food Diary" (optional completion)

From the time of recruitment to enrolling (first meeting) the volunteers will be able to calmly and carefully read the "INFORMATION AND CONSENT NOTE". The subjects may also request clarifications or details from the recruiter and/or the person in charge of the study. Moreover, before deciding, the volunteers will have time to ask an opinion to family or to a doctor of their trust.

The recruiters will make contact with the volunteers, collect the data and assign a code to the volunteer.

The standard data flow at the first, second and third meeting will be as follows:

First meeting:

1. Signed informed consent at the time of enrollment.

2. Compilation of the "Code sheet"

3. Withdrawal and control of the "food diary"

4. Filling in questionnaires

5. Anthropometric and arterial pressure measurements

Second meeting:

1. New notice of the information note and informed consent signature

2. Administration of the Food Frequency Questionnaire (FFQ) (http://www.sisdca.it/public/pdf/IDAO---testistica.pdf) with the aid of the Scotti Bassani portant atlas (http: // www .giorgiobedogni.it / archives / text / atlas / patlante.html)

3. Collection of saliva samples to assess their quality and for subsequent analysis

4. Delivery container for collection of urine and those for the collection of saliva for circadian cortisol.

Third meeting:

1. New notice of the information note and informed consent signature

2. Delivery of urine and saliva samples collected

3. Measurement of metabolic state parameters (cholesterol, triglycerides, glycemia and ketones)

An in-depth analysis of the lifestyle of Italian and Spanish university students will be carried out for the first time, with assessment of the frequency of self-medication and use of drugs and supplements/nutraceuticals. The composition of the oral microbiota in relation to eating habits will be determined for the first time. This study should also confirm the results of previous studies on the high rate of orthorexia in biomedical faculty students, especially among nutritionists and sports practitioners. The results of this study will also be useful for designing promotion programs for the correct use of drugs/supplements and for healthy diets and lifestyles in university students, and will also provide a potentially useful basis for the recruitment of subjects in additional/future intervention studies.

Condition or disease
Condition or disease: Medication Adherence
Location
Italy
Spain
Phase
-
Study design
Study type:Observational
Observational Model:Ecologic or Community
Time Perspective:Cross-Sectional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: June/30/2019
First Submitted: May/20/2019
First Posted: May/23/2019
Last Update Posted: July/17/2019
Sponsors: Vanderbilt-Ingram Cancer Center
Status: Recruiting
Description

Primary Objective:

• To evaluate the feasibility and tolerability of a 2 week ketogenic diet in combination with endocrine therapy prior to surgery for early stage ER+ breast cancer.

Secondary Objectives

- To determine whether endocrine therapy in combination with a dietary intervention to reduce insulin pathway signaling results in enhanced inhibition of cancer cell proliferation (measured byKi67)

- To determine the effectiveness of 2 weeks of a ketogenic diet to reduce measures of insulin/PI3Kpathway activation in breast tumors

- To measure changes in weight and body composition after 2 weeks of a ketogenic diet

- To measure changes in insulin resistance after 2 weeks of a ketogenic diet

- To measure the effectiveness of a ketogenic diet in combination with endocrine therapy to induce and maintain a ketogenic state.

Outline:

Participants will have baseline metabolic parameters measured and will begin a 2-week diet consisting of meal replacement shakes to induce a ketogenic state. Patients will also receive letrozole 2.5 mg daily. At the end of 2 weeks, metabolic parameters will again be measured and patients will proceed with surgical treatment of their breast cancer. A tumor biopsy from the surgical specimen will be obtained to measure cell proliferation compared with the pre-treatment diagnostic biopsy.

Condition or disease
Condition or disease: Estrogen Receptor-positive Breast Cancer
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:Female
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: December/31/2019
First Submitted: May/14/2019
First Posted: May/16/2019
Last Update Posted: January/29/2020
Sponsors: Daniel Bowers
Status: Not yet recruiting
Description

Primary Objective is to determine the feasibility (safety and tolerability) of a strict classic ketogenic diet among a population of children with recurrent or progressive and refractory brain tumors.

Secondary Objectives are: (1) to determine the objective response rate (complete response + partial response) to a strict classic ketogenic diet among children with recurrent or progressive and refractory brain tumor; (2) to estimate the time interval to tumor progression (Progression-Free Survival), time to treatment failure (Event-Free Survival), and time to death (Overall Survival) after initiation of a strict classic ketogenic diet among a group of pediatric patients with recurrent or progressive and refractory brain tumors; and (3) to describe and characterize tolerability and toxicities from a strict classic ketogenic diet among children with recurrent or progressive and refractory brain tumors.

Exploratory Objective: Identify biomarker correlates, including MR spectroscopy and metabolites of tumor response to a strict classic ketogenic diet.

Condition or disease
Condition or disease: Recurrent Brain Tumor, Childhood; Ketogenic Diet
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: June/30/2020
First Submitted: May/5/2019
First Posted: May/14/2019
Last Update Posted: July/16/2020
Sponsors: M.D. Anderson Cancer Center
Status: Recruiting
Description

Study Background:

Whole-foods, fiber-rich diet rationale: Recent studies have shown that the gut microbiome (the trillions of bacteria that live in our intestines) can influence our immune system function. Diet plays a key role in shaping the gut microbiome. We will examine the effects of a whole-food, fiber-rich diet on the gut microbiome within patients with a history of melanoma.

Ketogenic diet rationale: The ketogenic diet is a very-low-carbohydrate, high-fat diet. The goal of this diet is to change the body's fuel source from carbohydrates to fat and to lower levels of insulin. We will examine the effects of a ketogenic diet to change metabolism within patients with a history of melanoma.

Who can participate?

To be eligible for the study, participants must meet the following criteria:

- Be at least 18 years old;

- Meet the study requirements for Body Mass Index (BMI);

- Have had melanoma within the last 5 years;

- Be cancer-free at the start of the trial;

- Have not received systemic therapy within the last year; and

- Have no medical issues that would make them unable to follow these eating plans.

Study Design:

Our study will enroll up to 10 participants to each diet (high-fiber or ketogenic). After screening, participants will have baseline assessment performed that will include collecting diet information, blood and fecal samples, and body composition information. Participants will then eat the provided diets for the next 6 weeks while coming in every 2 weeks for blood and stool specimen collection. Six (6)weeks after the diet intervention is complete, participants will come back to MD Anderson for one last end of study visit.

Who makes the meals?:

All calorie-containing food and beverages will be provided by either the MD Anderson Cancer Center Bionutrition Research Core or Savor Health (a third-party vendor contracted by MD Anderson).

Costs: There will be no cost to participate in this study.

Benefits:

All food and beverages you will eat as part of this study will be provided by the study and can be shipped directly to your home. The results will be used to help us design future dietary intervention trials in Melanoma patients receiving immunotherapy. Please note, participants can withdraw from the study at any time without consequences.

Study PI: Dr. Jennifer McQuade

NCT#: NCT03950635

Contact Info:

Melanoma Medical Oncology (713)-792-5500 MelanomaDiet@mdanderson.org

Where: MD Anderson Cancer Center, Department of Melanoma Medical Oncology, Houston, TX

Condition or disease
Condition or disease: Melanoma
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: July/31/2019
First Submitted: December/19/2018
First Posted: December/23/2018
Last Update Posted: August/11/2019
Sponsors: Fred Hutchinson Cancer Research Center
Status: Terminated
Description

Little is known about the role of diet in the treatment of lung and other cancers, yet physicians are constantly confronted with the question 'what should I eat' by their patients. Very few randomized controlled dietary interventions have been carried out in this population, hence physicians and dietitians must use their best professional judgement to provide nutrition advice to their patients. Because most believe that nutrition is an important part of the treatment process, patients are eager to implement dietary recommendations and take control of this portion of their medical care. As such, upwards of 64% of patients use the internet to access health information related to cancer treatment with nutrition websites being among the most popular sites visited. However, the dietary advice on the internet aimed at cancer patients is highly discrepant, and even so among cancer treatment centers and research institutions. Within the National Comprehensive Cancer Network (NCCN), of which Fred Hutchinson is a member, only 43% (9 of 21 centers) either provide nutritional information on their website or linked to outside websites. Of those, roughly half recommended a low-fat diet during cancer treatment and the other half recommended a calorie-dense eating plan with the inclusion of high-fat foods. Clearly, this presents a potential pitfall for patients as they, without guidance from their physician or dietitian, may follow dietary advice that is misleading or potentially harmful.

While there is a need for further studies to elucidate the role diet plays during the treatment of cancers in general, lung cancer in particular is understudied in comparison to other types of cancers, and presents a unique opportunity to study the impact of diet during treatment. Primarily, lung cancer patients do not typically suffer from constraints to eating that affect colorectal, esophageal, or head/throat/neck cancer sufferers. Therefore, diet interventions using whole-foods may be fairly well tolerated in this population. A review of nutrition interventions in lung cancer patients carried out through October 2012 indicated that only three controlled studies in 149 patients had been completed, all of which used nutritional supplement products to prevent unintentional weight loss. The authors concluded that nutrition interventions in this population are safe and that more research is needed to determine optimal nutrition recommendations for advanced, inoperable lung cancers

. Through the manipulation of diet, it is possible to selectively target key pathways involved in cancer growth and proliferation. For instance, it is known that cancer cells generate energy through the process of anaerobic glycolysis (the Warburg Effect) which relies primarily on glucose as a fuel source. Evidence from in vitro studies of non-small cell lung cancer (NSCLC) suggests that reducing the glucose availability from the diet might be particularly effective in the treatment of squamous cell carcinomas because the glucose transporter (GLUT-1) expression is markedly elevated in these cancer cells and is associated with enhanced uptake of, and dependence upon, glucose. Case-control studies show that dietary glycemic index is strongly associated with squamous cell carcinoma among NSCLC patients, suggesting that dietary strategies that limit carbohydrate may be effective in 'starving' these predominately glycolytic cells. A diet pattern in which overall energy is not limited, but sources of glucose are selectively reduced, is one mechanism by which cancer progression might be abated. Such low-carbohydrate or - in their most extreme form - ketogenic diets, which provide energy primarily from fat and protein while minimizing carbohydrates, are increasingly shown to be therapeutic for the treatment of glioblastoma and other cancers, as well as neurological diseases, including epilepsy, and cardiovascular disease risk factors.

It is also known that activation of the IGF pathway is critical for tumor cell proliferation, invasiveness, and survival in NSCLC and downregulation of this pathway through dietary manipulation might also be an effective means to suppress cancer growth. The insulin-like growth factor-1 receptor (IGF-1R) is abundantly present on surfaces of tumor cells, and high circulating levels of IGF-1, the ligand for the IGF-1R, are a risk factor for future lung malignancy. As individuals who consume diets high in protein from animal sources have greater levels of circulating IGF-1 compared to those consuming a vegetarian/vegan diet, limiting the intake of animal products may be an intriguing dietary strategy that might influence cancer progression. In our lab, we have shown that insulin sensitivity and glucose tolerance improved after subjects adhered to a diet rich in whole grains, legumes, fruits, and vegetables, that excluded refined sources of energy (added sugar, refined grains, added fats and oils) (Kratz et al. unpublished data). This suggests that such a diet would also reduce the diurnal exposure of tumor cells to both glucose and insulin, which would decrease the availability of fuel and growth hormones for cancer cells. Taken together, both low-carbohydrate/ketogenic diets and low-fat, whole foods plant-based diets could plausibly affect pathways involved in cancer growth or progression by minimizing diurnal exposure to glucose, insulin, and IGF-1.

Condition or disease
Condition or disease: Diet Modification; Lung Cancer
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: May/31/2019
First Submitted: November/15/2018
First Posted: June/18/2019
Last Update Posted: June/20/2019
Sponsors: Universitaire Ziekenhuizen Leuven
Status: Recruiting
Description

Lymphedema is a debilitating disorder that severely impairs the quality of life of the patients and requires life-long attention. It can be classified as primary or secondary, based on the etiology. Primary lymphedema is a rare, congenital disorder caused by inherited genetic mutation on a number of genes that are essential for lymphatic vessel development and function. Acquired (or secondary) lymphedema is a consequence of lymphatic trauma, predominantly due to surgery or radiotherapy for various types of cancers, with axillary and/or inguinal lymph node dissection being the most common cause. At the cellular level, perturbed or dysfunctional lymphatic drainage triggers accumulation of interstitial fluid, negatively affects cellular behavior, and induces infiltration of fibroblasts, adipocytes and keratinocytes, eventually leading to possible fibrosis and ulceration.

Upper extremity lymphedema most commonly affects breast cancer patients, while lower extremity lymphedema is typically associated with gynecological cancers, prostate cancer, lymphoma and melanoma. Besides the functional impairments, lymphedema severely reduces the quality of life, causing psychosocial problems such as depression, sexual dysfunctions, social avoidance and a decrease in self-confidence. While the prevalence of lymphedema is relatively high (1.33-1.44 pro mille), its true prevalence is likely underestimated and 1 in 6 patients undergoing treatment for a solid tumor ultimately develops lymphedema.

Nevertheless, treatment for lymphatic dysfunction remains largely symptomatic, without real cure. According to the International Society of Lymphology, lymphedema has to be treated with Decongestive Lymphatic Therapy, a two-stage treatment program. During the first or intensive phase, lymphedema has to be maximally reduced: this phase consists of skin care, manual lymph drainage (MLD), multi-layer bandaging and exercise therapy. The second or maintenance phase aims to conserve and optimize the result obtained in the first phase, and consists of skin care, compression by a low-stretch elastic sleeve, exercises and MLD. Skin care, multi-layer bandaging, elastic sleeve and exercises are treatment modalities that can be performed by the patients themselves, after careful instruction from the physician. On the contrary, MLD has to be applied by a physical therapist and hence entails a big financial cost for the patient and the Health Care. In addition, reductive techniques, such as direct excision and liposuction, can be applied in patients with more advanced stages of lymphedema with a predominant fibrofatty component10. Encouraging initial results, i.e. symptomatic improvement and reduction in excess volume, have been obtained with lymphovenous bypass, the microsurgical anastomosis of collecting lymphatic vessels to adjacent venules, and vascularized lymph node transplantation, where lymph nodes are harvested from an unaffected region and transferred to the lymphedematous area. However, all the treatments available so far can offer only stabilisation of lymphedema and prevent further evolution, but they do not offer a definitive cure. There is thus a large unmet need to develop new effective therapies for lymphedema and, more general, lymph vessel dysfunction. In contrast to various strategies inhibiting lymphatic vessel growth, stimulating lymphatic vessel growth has been more challenging; there is currently no approved clinical strategy for ameliorating lymphatic dysfunctions. In this trial we will evaluate an entirely novel pro-lymphangiogenic strategy, not based on the delivery of lymphangiogenic growth factors, but rather based on modulating lymphatic endothelial cell metabolism. The lab of Angiogenesis and Vascular Metabolism (PCA lab), Catholic University Leuven, led by Prof. Peter Carmeliet recently reported that metabolism (glycolysis, fatty acid β-oxidation, glutamine metabolism) of endothelial cells, the cells lining blood vessels, controls vessel sprouting. Initial experiments from this PCA lab indicate that the Ketogenic Diet (KD) , which is effective in increasing the levels of ßOHB both in the plasma and lymph, ameliorates the disease outcome in the mouse (tail) model of lymphedema, by reducing edema formation over time. Strikingly, lymphangiography with Evans blue dye revealed that KD improves lymph vessel function, increasing dye uptake after subcutaneous injection in the lymphedematous tissue and its drainage into lymph, plasma and lymph nodes.

Based on these proof-of-concept data, the investigators plan to test this innovative concept to ameliorate lymph vessel dysfunction in lymphedema patients. Randomisation will be performed between a ketogenic diet and a isocaloric diet. After randomization and baseline measurements (determination of energy requirements and intake), the intervention will consist of 3 phases: a one week run-in period, 24 weeks strict KD and 24 weeks Modified Atkins Diet. In the first phase, the one week run-in period, is establishment of the individual ketosis level (on average after five days ketosis is introduced). During this run-in period, the exact ratio of lipids over proteins and carbohydrates will be determined per patient based on an isocaloric diet; this ratio will vary per patient and over time. Every day, 40 g of KetoCal, a nutritionally complete ready-to-drink liquid, is foreseen to ensure adequate amounts of vitamins and minerals and to ensure ketosis during the night (some patients drink some sips of the shake during the night). During this run-in period, patients will become familiar with their diet and, in particular, they will learn which foods are allowed and which are not. To assist the patients, the ketobel program (a computer program developed by the metabolic dieticians of the Clinical Nutrition Unit, University Hospital Leuven) will allow the calculation of the exact amount of foods/lipids each patient can/needs to consume. The instructions given by the program will allow patients to create a menu according to their personal preferences, with the final aim of increasing the adherence to the KD. A dietician will assist every participant intensively in this run-in period (10 h/week). To ensure ketotic state, ketosis will be measured twice a day (morning and evening) using urinary sticks. If there is a change in the ketotic state, the lipid/non-lipid fraction ratio will be adjusted in collaboration with the dietician.

In the second phase, 24 weeks of strict KD , the patients will receive 40 g of KetoCal daily and the dietician will assist the patient during this phase 2 hours/week. This support is necessary as the lipid/non-lipid ratio to obtain ketosis varies over time as well. In the second phase, the dietician will assess on a weekly basis general health status, body parameters (weight, waist circumference), physical activity, weight loss and compliance to diet. The plasma metabolite profile (different types of cholesterol, triglycerides, fasting glucose, hsCRP, ketone bodies) will be performed every 3 weeks. To stimulate adherence to the diet, chat sessions will be organized between patients and a dietician, as moderator; these sessions will take place once a week and allow patients to exchange ideas/recipes about the diet and to motivate each other. These chat sessions have been organized previously by the members of the Clinical and Experimental Endocrinology group in other projects and were considered by the patients as an added value and a stimulation to continue with the intervention.

In the third phase, the patients' diet will be less strict and adapted to a Modified Atkins Diet. This shift is necessary to enhance adherence on the one hand and to allow follow-up for a longer period.

During the run-in period, the energy requirements and intake of the control group will be assessed as well. During this run-in period, the dietician will discuss the diet and maintenance of an isocaloric diet with the patients. As such, the diet of the control group will not change from their normal dietary pattern, unless a patient is following an Atkins-like diet. In the latter case, the patient will be asked to change the diet to a normal Belgian diet. During the first 24 weeks of intervention period, the patients will be contacted every 3 weeks to stimulate the participants and to follow up on some basic anthropometric markers, such as weight and waist circumference. The dietician will also adapt, if needed, the isocaloric diet of the control group during the intervention period to match possible unwanted weight loss of patients in the KD group. In the third phase of the study, patients will not be contacted outside the standard of care and the data will only be collected after 48 weeks.

Condition or disease
Condition or disease: Lymphedema; Ketogenic Dieting
Location
Belgium
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: April/30/2020
First Submitted: May/8/2018
First Posted: May/23/2018
Last Update Posted: May/31/2020
Sponsors: Ohio State University Comprehensive Cancer Center
Status: Recruiting
Description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of implementing a diet that induces nutritional ketosis in women who are initiating palliative chemotherapy to treat advanced stage breast cancer (BC).

II. To determine the effects of a ketogenic diet on tumor progression. III. To determine the effects of nutritional ketosis on biologic and behavioral health markers.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive standard of care therapy with paclitaxel.

ARM II: Patients receive standard of care with paclitaxel. Patients undergo a controlled feeding period ketogenic diet comprising of meals prepared in the research kitchen for 3 months. Beginning 2 weeks prior to completion of the controlled feeding period, patients also undergo free living ketogenic diet program for 3 months comprising of group format, individual sessions, and online digital content to educate patients to implement a ketogenic eating pattern into their lifestyle.

Condition or disease
Condition or disease: Stage IV Breast Cancer AJCC v6 and v7
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
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1
Posts:
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Clinical trial
Last Verified: December/31/2018
First Submitted: April/16/2018
First Posted: April/26/2018
Last Update Posted: January/14/2019
Sponsors: Yonsei University
Status: Recruiting
Abstract

Decreased bowel function and loss of appetite in patients who underwent pancreaticobiliary surgery contribute impaired nutritional status in postoperative period. It can also affect perioperative and oncologic outcomes negatively. Therefore it is important to improve nutritional status in postoperative period by supply tailor-made optimal diets. The investigators have developed customized postoperative diets and products for pancreaticobiliary cancer patients. This time, newly developed ketogenic drink contain beefsteak mint.

The investigators expect that nutritional supplement for pancreaticobiliary patients will increase the food intake rate and contribute a improvement of perioperative outcomes and even oncologic outcomes.

Condition or disease
Condition or disease: Pancreaticobiliary Cancer
Location
Korea, Republic of
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:19 Years to 19 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2020
First Submitted: February/25/2018
First Posted: March/1/2018
Last Update Posted: April/8/2020
Sponsors: Jethro Hu
Status: Recruiting
Description

Enrolled subjects will be placed on a 16-week ketogenic diet (subject specific as prescribed by RD) while receiving standard of care cancer treatment (Radiation + Temozolomide). Study dietitians will place patients on a strict and controlled diet that manages daily macronutrient breakdown and increases the ratio of dietary fat relative to protein and carbohydrate consumption. Dietitians will provide guidance and teaching of the diet, as well as, monitoring and diet adjustment to ensure metabolic ketosis. Dietitians and study physicians (and their staff) will monitor subjects for safety, nutrition, quality of life, and standard of care tumor assessments over the course of the study.

Condition or disease
Condition or disease: GBM; Glioblastoma
Location
United States
Phase
Phase 1
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: March/31/2019
First Submitted: February/22/2018
First Posted: March/8/2018
Last Update Posted: April/17/2019
Sponsors: University of British Columbia
Status: Completed
Description

The potential for a ketogenic diet to reduce inflammation has become increasingly popular in recent years, but direct scientific evidence to demonstrate that ketones impact inflammatory mechanisms in humans does not exist. B-hydroxybutyrate (B-OHB) is the most abundant circulating ketone and recent evidence indicates that B-OHB may be able to act as a direct signal to inhibit cellular pathways involved in inflammation.

B-OHB can be raised naturally by induction of nutritional ketosis, which is a normal physiological response to severe reductions in carbohydrate or caloric intake. In this state, free fatty acids are converted to ketone bodies (primarily B-hydroxybutyrate [B-OHB]) by the liver in order to provide essential fuel for metabolically active tissues. However, determining the direct effects of B-OHB in human ketogenic diet studies is difficult due to the numerous metabolic adaptations that occur in nutritional ketosis (e.g., reduced insulin, elevated free fatty acids, stable glucose) and the propensity for participants to lose body and fat mass over longer period.

B-OHB can also be raised independent of diet by supplementation with medium chain triglyceride (MCT) oil, allowing for induction of ketosis without the additional metabolic adaptations. In addition to being an important fuel source, recent interest has focused on a potential signaling role for B-OHB with cell culture and animal studies describing anti-inflammatory, anti-oxidant, and anti-cancer effects. The cellular pathways through which B-OHB is proposed to reduce inflammation, include the NLPR3 inflammasome and histone deacetylases (HDACs), both of which play important roles in regulating cellular inflammation. The NLRP3 inflammasome pathway is an immune complex which, upon activation, initiates downstream pro-inflammatory cascades including the activation of caspase-1 and interleukin (IL)-1B. These pro-inflammatory cascades have been implicated in the propagation of sterile inflammation, which has been identified as a major contributor to certain chronic inflammatory diseases such as type 2 diabetes and atherosclerosis. HDACs are enzymes typically found within the nucleus and have the ability to regulate signaling through innate immune pathways. B-OHB has been shown to have the ability to inhibit HDACs, and consequently has the potential to decrease oxidative stress and inflammation. The NLRP3 inflammasome and HDACs are responsive to the intracellular nutritional milieu and thus their activity may be able to be modulated through increases in B-OHB.

The use of MCT oil supplements will allow the investigators to raise blood B-OHB independent of diet, and thus directly test the immunomodulatory effects of B-OHB in healthy, adult males. This fundamental research is needed to understand whether ketones have direct immunomodulatory effects or if it is the widespread systemic metabolic adaptation to a ketogenic diet that might impact inflammatory processes.

The overall objective of this pilot study is to determine if directly raising B-OHB through supplementation with MCT oil impacts innate immune cell function and/or phenotype. Based on previous cell culture and animal research showing that B-OHB can reduce pro-inflammatory signaling, it is hypothesized that raising B-OHB with MCT oil supplementation will result in a attenuation of caspase-1 activation and mature IL-1B secretion, both markers of NLRP3 inflammasome activation. Additionally, it is hypothesized that raised B-OHB will result in greater histone acetylation, as B-OHB has been shown to be an HDAC inhibitor.

Condition or disease
Condition or disease: MCT Oil Supplementation
Location
Canada
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Pulse
Views:
1
Posts:
No posts
Rating:
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Clinical trial
Last Verified: December/31/2019
First Submitted: October/22/2017
First Posted: October/31/2017
Last Update Posted: February/4/2020
Sponsors: Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Status: Terminated
Description

Brain tumors account for nearly 20% of all childhood malignancies. Of these, gliomas represent 50% of all brain tumors in children and young adults. Gliomas are classically divided into two subtypes - low-grade and high-grade. Low-grade gliomas (LGG) include pilocytic astrocytomas and diffuse astrocytomas, and high-grade gliomas (HGG) include anaplastic astrocytoma and glioblastoma multiforme. Although patients with grade I and II tumors have a good prognosis with 5-year overall survival rates of 80-90%, those cases that are recurrent, refractory, and/or unresectable remain a challenge. The prognosis of children and young adults with recurrent or refractory malignant brain tumors remains poor despite dramatic improvements in treatment over the past few decades, with only a minority achieving long-term survival if recurrence occurs following initial surgical resection and adjuvant chemotherapy.

For patients with HGG prognosis remains dismal despite aggressive treatment. In this subset of patients, the 5-year overall survival for anaplastic astrocytoma ranges from 20-40% and for glioblastoma 15-20%. Diffuse intrinsic brain stem gliomas (DIPG) have the worst overall prognosis with a nine-month mean overall survival and with most patients dying from the disease within 2 years. Thus, the development of new treatment protocols for children and young adults with both high grade gliomas and with recurrent or refractory low grade gliomas is crucial to improving the survival rates of these patients.

The Ketogenic Diet (KD) has been in clinical use for nearly a century, initially designed to mimic the effects of starvation. Over the last two decades metabolic studies have been gaining momentum as increasingly promising in disease modification of central nervous system disorders and tumors.

Tests in animals and studies in adult patients with brain tumors have shown that there are advantages to using the ketogenic diet. These include: improved response of the tumor to standard treatment (chemotherapy/radiation) and improvement in quality of life measures (alertness).

Condition or disease
Condition or disease: Brain Tumors
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:12 Months to 12 Months
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: August/31/2019
First Submitted: October/5/2017
First Posted: October/22/2017
Last Update Posted: September/15/2019
Sponsors: Johns Hopkins University
Status: Terminated
Description

1. Abstract Epilepsy affects a significant number of children in the United States. The majority of patients achieve control of their seizures by conventional treatment strategies including medications. However, one third of patients do not achieve satisfactory seizure control with medications alone. Ketogenic diet and lifestyle modifications may also be tried. In some of these children, the seizure focus can be localized to one area of the brain and the seizures are resistant to conservative treatment strategies. These children may have subtle structural/developmental abnormalities in their brain, the most frequent of which is focal cortical dysplasia. These are localized areas of abnormal lamination of the cerebral cortex that can be extremely subtle and difficult to detect, even with state of the art magnetic resonance imaging (MRI). More importantly, these lesions may be amenable to surgical resection resulting in marked decrease in frequency or even resolution of seizures.

MRI is a noninvasive imaging modality without ionizing radiation that has played a central role in the assessment of anatomy, physiology/pathophysiology of children with epilepsy. It is particularly useful in children with refractory focal epilepsy. Prior studies have shown that high resolution, high-field (3T) MR imaging of the brain helps to identify subtle focal epileptogenic abnormalities, including focal cortical dysplasia, in some patients. However, there is scarce data directly comparing the performance of ultra high-field (7T) MRI, currently an investigative technique offering optimized contrast and signal-to-noise rations and superior spatial resolution, with clinically available 3T MR imaging.

The purpose of this study is to evaluate whether ultra high-field (7T) MR imaging improves detection and characterization of subtle structural epileptogenic abnormalities in children with focal epilepsy.

The importance of this research is that identification of a focal epileptogenic lesion in children with refractory epilepsy has fundamental management implications, as surgical removal of such lesion may dramatically improve outcomes and the chance of seizure freedom.

2. Objectives (include all primary and secondary objectives)

The objectives of Investigators' project are:

To evaluate the performance of 7T MRI in detecting structural abnormalities in children who have had 3T MRI-negative focal epilepsy.

To characterize conventional and advanced neuroimaging features of epileptogenic lesions such as cortical dysplasias and neuroglial tumors at 7T MRI.

3. Background High-resolution brain MRI is currently an integral component in the diagnostic evaluation of children with focal epilepsy. When focal epileptogenic abnormalities are identified, such as cortical dysplasia, the management strategy includes evaluation for potential surgical resection, which may dramatically improve outcome. The current clinical state of the art of 3T MRI has superior sensitivity over conventional 1.5T MRI. However focal cortical dysplasia remains one of the most common pathological diagnoses after pediatric epilepsy surgery, even when not detected by current MRI exams.

4. Study Procedures

1. Study design, including the sequence and timing of study procedures. The investigators plan to perform 7T brain MRI in children with the diagnosis of epilepsy and findings on EEG suggestive of a focal structural abnormality. The 7T MRI exams will be performed at Kennedy Krieger Institute (KKI) as part of their outpatient evaluation. The investigators plan to accrue approximately 50 participants.

Before recruiting children with epilepsy, approximately 2-10 healthy adult volunteers will be recruited for the purpose of optimizing the imaging acquisition protocol. These adults will be consented using a separate consent form, also attached to this application.

Children will be eligible if they have already had a 3T MRI examination and do not have any contraindications to MR examinations. A consent form signed by the patients' parent/legal care giver will be required to indicate agreement to participate in the study. In addition, a consent form signed by the patient (if over 15 year of age) or an assent form signed by the patient (if between 8-15 years of age) will be required to indicate agreement to participate. Patient charts will be reviewed for history and diagnosis.

2. Study duration and number of study visits required of research participants. The anticipated duration of this study will be 2-5 years beginning in April 2017. The 7T MRI exam will be performed in a single visit. This project may involve one additional trip to the hospital for patient subjects.

3. Blinding, including justification for blinding or not blinding the trial, if applicable.

N/A

4. Justification of why participants will not receive routine care or will have current therapy stopped.

N/A

5. Justification for inclusion of a placebo or non-treatment group. N/A

6. Definition of treatment failure or participant removal criteria. Removal criteria will be defined as participants who are unable to tolerate the MR procedure due to previously unknown claustrophobia, inability to tolerate lying still for the exam period, or due to presence of ferromagnetic implants preventing imaging.

7. Description of what happens to participants receiving therapy when study ends or if a participant's participation in the study ends prematurely.

Not applicable. This is not a treatment study.

Data collection and management will be implemented with the following guidelines to ensure their confidentiality and safety:

1. Confidentiality of Data: A master list separate from data forms that have only a study number will be used to maintain confidentiality of data.

2. Security: The master list and backup copy will both be kept only on secure Johns Hopkins computers. Only de-identified data will be stored on a non-Johns Hopkins personal computer.

3. Anonymization: The identifiers will be destroyed after publication. The other data will be retained for three years.

4. Confidentiality: All data and records generated during this study will be kept confidential in accordance with Institutional policies and HIPAA on subject privacy and that the Investigator and other site personnel will not use such data and records for any purpose other than conducting the study. Safeguards are described under Data Collection and Management.

5. Inclusion/Exclusion Criteria

a. Inclusion Criteria i. Male or female children between 6-21 years of age undergoing an MRI for focal epilepsy at the Johns Hopkins Hospital OR ii. Adult healthy volunteer. iii. Willing to undergo an additional MRI exam in the 7T scanner at Kennedy Krieger Institute.

b. Exclusion Criteria i. Presence of any contraindication to MR examinations as defined by MRI Safety Screening Sheet ii. History of Metal in the Skull/Eyes iii. Pregnancy at the time of the scan iv. Patient subjects in unstable clinical condition

6. Drugs/ Substances/ Devices

1. The rationale for choosing the drug and dose or for choosing the device to be used.

Only patients with a clinical indication for brain MRI examination will undergo 7T MRI. All examinations will be performed without intravenous contrast and in an outpatient setting, without the need for deep sedation or general anesthesia. Although classified by FDA as an investigational device, the 7T MR system has been ruled as a non-significant risk device by the same agency. This finding is stipulated in Guidance for Industry and FDA Staff --Criteria for Significant Risk Investigations of Magnetic Resonance Diagnostic Devices issued July 14, 2003. A copy of the ruling has been uploaded in Section 3.0 for your review. In well over 1000 studies done at 7T in the last decade at multiple institutions (University of Minnesota, Massachusetts General Hospital, NIH), no significant risks have been found. Some subjects have experienced dizziness. A potential concern with MR studies at high fields is radiofrequency heating due to radiofrequency power deposition in the subject. The FDA has set strict guidelines to guard against this risk. Such power deposition increases with the square of the magnetic field strength. However, even at 7T it is possible to stay well within these guidelines, especially with the pulse sequences the investigators will employ. To be 100% sure of compliance with FDA guidelines, the software of the manufacturer monitors power deposition continuously and scans are not possible to implement if the power deposition would exceed guidelines.

Documents have been uploaded in Section 3.0 regarding federal guidelines supporting the position that a 7 Tesla MR scanner represents no significant risk to human subjects.

Theoretical concepts and prior clinical studies justify the interest in applying high-resolution, ultra high-field MRI as a tool to evaluate detailed brain anatomy and physiology in children with focal epilepsy. Most studies comparing the diagnostic yield of 3T versus 1.5T imaging in detecting structural lesions in patients with focal epilepsy reached positive conclusions concerning the rates of newly detected lesions at 3T Very few comparative studies have investigated the diagnostic yield of 7T with respect to conventional MRI, however these included both examinations performed at 1.5T and at 3T.

The employment of 7T MRI provides superior capability in characterizing anatomical and physiological brain parameters. In collaboration with MR physicists affiliated with Johns Hopkins and with Kennedy Krieger Institute, our imaging acquisition protocol should include:

- High-resolution anatomical sequences, such as volumetric T1-weighted MP2RAGE and 2D gray-white tissue border enhancement (TBE) Fast Spin Echo (FSE)-Inversion Recovery (IR). These images are optimal for evaluating the interface between the cortex and the juxtacortical white matter when attempting to detect subtle focal cortical dysplasias, an important cause of focal refractory epilepsy in children.

- Susceptibility-weighted imaging. 7T has been shown to offer superior sensitivity in detecting abnormal blood products and iron deposition in the cerebral parenchyma, in addition to the exquisite depiction of the normal and abnormal cerebral venous anomaly. These images may also be used for subjective evaluation of oxygen extraction fraction in the brain, and for quantitative mapping of iron deposition.

- Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Both techniques explore the diffusivity of water molecules in the intra- and extracellular spaces of the brain, along with the directionality of movement. The acquisition generates parameters of white matter integrity and anisotropy, including mean diffusivity, longitudinal and radial diffusivity, and fractional anisotropy. With this information, detailed in vivo maps of white matter fibers (tractography) can be produced, as well as maps of anatomic connectivity (connectome). DKI is a novel diffusion imaging technique that explores the non-Gaussian distribution of white matter molecules and is able to further characterize the complexity of white matter microstructure. DKI has thus far been scarcely explored in the study of pediatric neurological disorders.

- Resting-state functional MRI. Several studies have shown disturbance of functional pathways in children with focal refractory epilepsy. This technique relies on the blood-oxygen level dependent (BOLD) effect, does not require tasks as in other Functional MRI (fMRI) acquisitions, and can be postprocessed to generate maps of functional connectivity.

- MR Spectroscopy (MRS): 1H MRS is a noninvasive imaging technique that can easily be added to the conventional MRI sequences and is able to measure metabolism in the brain. Metabolic changes arising from pathology that can be visualized by MRS may not be apparent from anatomy. During a seizure, the metabolic demands exceed the supply of oxygen and nutrients to the portion of the brain that is undergoing the enhanced electric activity. Under these circumstances, metabolic changes can be detected by MRS, including the production of lactate and, if prolonged, the reduction of N-Acetyl Aspartate (NAA), and an increase in Cho. These abnormalities can still be observed after seizure activity ceases. Another common clinical scenario for the use of MRS is temporal-lobe epilepsy (TLE) to help localize the source of the seizures.

Images acquired from 7T MRI examinations will not be used in isolation to guide patient care. In the event that 7T discloses a focal structural abnormality of the brain that was not detected at 3T MRI, this finding will be evaluated by a multidisciplinary team responsible for care of the particular patient. Management decisions will then be suggested to the patient and family considering all the clinical, electrographic, and neuroimaging data available.

2. Justification and safety information if FDA approved drugs will be administered for non-FDA approved indications or if doses or routes of administration or participant populations are changed.

Not applicable.

3. Justification and safety information if non-FDA approved drugs without an Investigational New Drug (IND) will be administered.

Not applicable.

7. Study Statistics

1. Primary outcome variable. The primary outcome variable is the sensitivity of 7T brain MRI in the detection of subtle cortical abnormalities in children with focal epilepsy.

2. Secondary outcome variables. The secondary outcome variables include subjective characterization of subtle epileptogenic lesions, and quantitative metrics from advanced MR sequences such as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) may be obtained from DTI sequences. Quantitative parameters may also be obtained from other imaging techniques such as MR spectroscopy.

3. Statistical plan including sample size justification and interim data analysis. N/A

4. Early stopping rules. N/A

8. Risks

1. Medical risks, listing all procedures, their major and minor risks and expected frequency.

All participants will undergo the informed consent process. Children over the age of 15 will be asked to document their consent by signing the consent form. Children between the ages of 8 and 15 years of age will be asked to indicate their assent by signing the assent document. Assent will be obtained for children <8 years of age by monitoring visual and vocal indications as well as body language. Parents of all children will be asked to document their consent of the procedure on the consent form.

The effects of magnetic fields in an MRI scanner have been extensively studied, and there are no known risks with an MRI exam. Participants may, however, be bothered by feelings of confinement (claustrophobia), and by the noise made by the image acquisition during the procedure.

2. Steps taken to minimize the risks. Participants will be asked about contraindications to MR examinations (as outlined by the MRI screening sheet). Participants will wear earplugs and earphones while in the magnet. Participants may not participate in this study if they have a pacemaker, an implanted defibrillator or other implanted electronic or metallic devices.

3. Plan for reporting unanticipated problems or study deviations. Adverse events, unanticipated problems, and study deviations will be reported to the IRB in writing by study personnel within 5 days of learning of the event. Serious adverse events will be reported immediately.

4. Legal risks such as the risks that would be associated with breach of confidentiality.

There are no known or anticipated legal risks associated with participating in this study.

5. Financial risks to the participants. There are no known or anticipated financial risks associated with participating in this study.

9. Benefits

a. Description of the probable benefits for the participant and for society. i. Individual participant

Individual participants may benefit by receiving higher end, non-invasive, non-contrast MR imaging studies that may (or may not) increase sensitivity and specificity of diagnosis and prognosis.

ii. Society Society may benefit if investigators are able to establish the value of 7T MR imaging in focal pediatric epilepsy. By developing a high-resolution 7T brain MRI protocol for pediatric epilepsy, the data obtained from these exams may serve as the basis to alter diagnostic workup. This may ultimately improve early detection and characterization of lesions, and guide surgical planning, and may facilitate better outcomes.

10. Payment and Remuneration

a. Detail compensation for participants including possible total compensation, proposed bonus, and any proposed reductions or penalties for not completing the protocol.

All studies will be performed in addition to a clinically indicated MRI appointment. No additional costs or billing will be generated to the patients. Subjects may receive a copy of their images on compact disc upon request.

11. Costs a. Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify who will pay for them.

Patient subjects will not incur any additional costs directly related to their participation in this project. The 7T MRI exams will be funded by a research grant.

Condition or disease
Condition or disease: Epilepsy
Location
United States
Phase
-
Study design
Study type:Observational
Observational Model:Case-Only
Time Perspective:Prospective
Eligibility Criteria
Ages Eligible for Study:6 Years to 6 Years
Sexes Eligible for Study:All
Sampling method:Non-Probability Sample
Accepts Healthy Volunteers:No
Clinical trial
Last Verified: April/30/2020
First Submitted: September/13/2017
First Posted: September/14/2017
Last Update Posted: June/3/2020
Sponsors: Memorial Sloan Kettering Cancer Center
Status: Recruiting
Abstract

The purpose of this study is to test any good and bad effects of an experimental diet, called a ketogenic diet, in endometrial cancer. A ketogenic diet is one that is very low in carbohydrates (simple and complex sugars). The goal of this diet is for the body to go into a state of ketosis. Ketosis is when the body does not have enough sugar for energy so it burns stored fats which create acids called ketones, which can be used for energy. Researchers hope to learn whether or not a ketogenic diet is well-tolerated and safe to eat before surgery in endometrial cancer patients.

Condition or disease
Condition or disease: Endometrial Cancer
Location
United States
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:Female
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: July/31/2017
First Submitted: May/21/2017
First Posted: May/30/2017
Last Update Posted: August/9/2017
Sponsors: University of Alabama at Birmingham
Status: Completed
Description

This investigation is a randomized, controlled clinical trial among 66 (for a final n of 50) women with ovarian and endometrial cancer. Patients are randomized to one of two study arms for 12 weeks: usual care plus the ketogenic diet (KD) or usual care plus dietary recommendations endorsed by the Academy of Nutrition and Dietetics (AND).

Cases are accrued in the University of Alabama at Birmingham gynecologic oncology clinic. Patients are then randomized to one of the two diet groups using a blocked randomization strategy. The prescription for the AND follows the Academy's 2013 guidelines, with modifications as necessary of ovarian cancer. The KD has a macronutrient composition of ~5% energy from carbohydrate, 25% energy from protein, and 70% energy from fat. Carbohydrate foods include non-starchy vegetables (e.g., salad greens, green beans, summer squash). Patients are advised to avoid refined starches and added sugar and to emphasize consumption of whole foods. Protein foods include meat, poultry, fish, and eggs. Because protein can be converted to glucose in the liver via gluconeogenesis, patients are counseled to eat no more than ~100g protein per day, distributed across the day. Fat-containing foods include olive, coconut, and nut oils; butter; tree nuts and nut butters; cheese; cream; coconut milk; and avocados. Patients are counseled to obtain the majority of their fat intake from mono-unsaturated fatty acids (e.g., olive oil), and medium-chain triglycerides (e.g., coconut oil and milk); from nuts and nut butters; and from fresh fish. Full-fat dairy is limited to 4 ounces of cheese per day; butter is not limited. This diet is formulated to be low glycemic and anti-inflammatory, thereby lowering glucose, insulin, and markers of inflammation. Total energy intake is not restricted, as the focus is on insulin reduction rather than weight loss.

Diet interventions are provided by registered dietitians at the University of Alabama at Birmingham. Participants meet one-on-one with a dietitian at the baseline testing visit. Patients record food intake such that the dietitian can review them on a weekly basis, provide feedback, and tailor nutrition counseling; said counseling is delivered via phone and e-mail on a weekly basis throughout the 12-week intervention. Food records are analyzed for macronutrient composition, a range of micronutrients, and glycemic index.

Outcome measures include demographics (age, sex, race); body composition by dual X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA); fasting concentrations of markers of inflammation, cancer progression (CA-125), and metabolism (glucose, insulin, ketones); cancer progression (as measured by CT scans done as part of usual care); quality of life (as measured by the Medical Outcomes Study Short Form-12 Health Survey, SF-12); satiety (as measured by a visual analog scale, VAS); and food cravings (as measured by the Food Craving Inventory, FCI).

Within groups changes in cancer markers, body composition, and other outcomes will be evaluated with paired t-tests. Between group differences will be evaluated with ANOVA/ANCOVA, controlling for relevant confounders (e.g., baseline values, age). Correlation analysis will be used to test the specific hypothesis that decrease in cancer outcomes across all patients will be associated with increase in serum ketone concentrations and decreasing concentration of fasting insulin. In a pilot study of 10 cancer patients, all of whom were placed on a KD, serum ketone production was increased to a greater extent (P<0.02) in those patients who showed remission or stable disease than in those patients who showed continued disease progression (Fine et al., 2012). Further, change in ketone production was associated with change in fasting insulin concentration. Thus, sample size calculations were based on change in fasting insulin using a previous diet intervention in a population of overweight/obese women with PCOS (Gower et al. 2013). In this study, a decrease in fasting insulin of 2.7 ± 4.6 µIU/ml was observed after 8 weeks of consumption of a eucaloric reduced-carbohydrate diet. Assuming a change of 2.7 ± 4.6 (µIU/ml), a two-sided paired t-test, and a significance alpha level of 0.05, we would have over 80% power to detect a significant change in fasting insulin with 25 participants per diet group. Allowing for 30% attrition, we plan to recruit 33 participants per diet group (total n=66).

Hypotheses include: 1) Cancer outcomes will improve in the KD group relative to the AND group, 2) The KD group will show a selective loss of visceral fat and preservation of lean mass, 3) Fasting concentrations of glucose, insulin, and insulin-like growth factor 1 (IGF-1) and its binding protein (IGFBP-1) will decline in the KD group but not in the AND group, 4) Changes in serum insulin concentration will be directly associated with changes in the cancer marker CA-125, 5) Changes in serum ketone concentration will be inversely associated with changes in cancer marker CA-125, and 6) Ratings of quality of life, food cravings, and satiety/hunger will improve in the KD group but not in the AND group.

Condition or disease
Condition or disease: Ovarian Cancer; Endometrial Cancer
Location
-
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:19 Years to 19 Years
Sexes Eligible for Study:Female
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: August/31/2018
First Submitted: May/1/2017
First Posted: May/18/2017
Last Update Posted: September/4/2018
Sponsors: Second Affiliated Hospital of Guangzhou Medical University
Status: Recruiting
Abstract

Malignant tumor incidence showed an upgrade trend in recent years. Standard therapy for malignant tumor includes surgery followed by radiation and chemotherapy. Despite optimal treatment the prognosis remains poor. There is an urgent need for more effective therapies. The Warburg effect has been widely observed in human cancers. The main energy supply of tumor cells are aerobic glycolysis. Therefore, they are highly dependent on glucose metabolism. Recently, some scholars have suggested that 'Restricted calorie Ketogenic Diet (RKD)' might be able to inhibit glycolysis and thus anti-tumor by restricting carbohydrate intake. This will 'starve' cancer cells, which will lead to cell death. There are many animal and in vitro studies shown that RKD can reduce the tumor size and thus tumor cell growth of malignant tumors. However, a consistent positive result can not be found within a small sample of clinical trials. In this study, 40 patients with malignant tumors will be treated with or without RKD. The safety and efficacy of RKD and the patients' tolerance will be observed in order to understand whether this therapy can be a potential new treatment This clinical study is comparatively large internationally. It is the first domestically. This study is essential to extend the survival of patients with malignant tumors, and to study clinical nutrition support and its metabolic pathways for malignant tumors.

Condition or disease
Condition or disease: Malignant Tumors
Location
China
Phase
-
Study design
Study type:Interventional
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:All
Accepts Healthy Volunteers:Yes
Clinical trial
Last Verified: February/29/2020
First Submitted: April/20/2017
First Posted: June/20/2017
Last Update Posted: March/16/2020
Sponsors: University of Maryland, Baltimore
Status: Active, not recruiting
Description

More than 1.6 million new cases of cancer are estimated in the United States in 2016, with almost 600,000 individuals dying from the disease. Prostate cancer alone is responsible for 180,000 new diagnoses per year and remains the most common new cancer diagnosis for men.

Current treatment options for prostate cancer include surgery, radiation, high-intensity focused ultrasound, and cryotherapy. Although typically successful, these strategies carry significant risks for incontinence, erectile dysfunction, and local tissue injury. As a result, for a select subgroup of men with more indolent forms of prostate cancer, active surveillance has become the preferred management strategy. This approach entails periodic laboratory testing, with prostate-specific antigen (PSA) checks at intervals of 3-6 months, and repeat prostate biopsies every 1-2 years or earlier if indicated by PSA elevations. Treatment interventions are typically withheld unless re-biopsy results indicate progression to more aggressive disease. Prospective data comparing surgery and active surveillance have demonstrated improved quality of life outcomes with the latter approach . Not surprisingly, national registry data shows that active surveillance usage has increased from <15% between 1990 and 2009 to >40% between 2010 and 2013 for eligible patients . In order to ensure proper patient selection for active surveillance, MRI guided confirmation biopsies have become standard of care options. Almost one-third of patients will be found to harbor more aggressive cancer than revealed by their initial biopsy. Ideally, treatment could be delayed indefinitely for properly selected patients.

Although surveillance offers a reprieve from cancer treatment and its potential negative sequelae, this benefit appears temporary for many men. Institutional cohort data indicate that 36%-55% of men on active surveillance will require treatment for disease progression within 10 years. One notable risk factor for disease progression during surveillance is overweight and obesity. In a study of 565 prostate cancer patients on surveillance, a 50% increased risk of pathologic progression was associated with every 5 kg/m2 increase in BMI over 25. These results support additional evidence linking weight gain with an increased risk of prostate cancer recurrence after surgery. They have also prompted studies examining pre-surgical weight loss using caloric restriction to mitigate the risk associated with obesity. A low carbohydrate, ketogenic approach has been previously studied in small samples of patients with other types of cancer and also proposed for prostate cancer patients.

In brief, a ketogenic diet is a high-fat, low-carbohydrate diet that mimics the metabolic state of long-term fasting. Ketone bodies are generated mainly by ketogenesis in the mitochondrial matrix of liver cells and are subsequently exported via the blood to other organs to cover the energy demands of cells throughout the body. Ketogenic deaminated amino acids such as leucine also feed the citric acid cycle to form ketone bodies. Utilization of a ketogenic diet as an adjuvant prostate cancer therapy is particularly intriguing given recent preclinical data demonstrating that ketones function as endogenous histone deacetylase (HDAC) inhibitors. HDAC inhibitors have been shown to inhibit prostate cancer proliferation in preclinical models, and are already being studied in clinical trials. Therefore, the ketogenic diet may have a direct impact on disease progression that may extend beyond the BMI reduction achievable by caloric restriction, exercise or other weight loss strategies.

Condition or disease
Condition or disease: Prostate Cancer
Location
United States
Phase
-
Study design
Study type:Observational
Observational Model:Case-Only
Time Perspective:Prospective
Eligibility Criteria
Ages Eligible for Study:18 Years to 18 Years
Sexes Eligible for Study:Male
Sampling method:Probability Sample
Accepts Healthy Volunteers:Yes
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