The KetoGlioma (Ketogenic Glioma) Study

Study Overview
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Brief Summary
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This research is being conducted to see if patients diagnosed with high grade gliomas can adhere to the supplemented High-Fat Low-Carbohydrate (sHFLC) + KetoPhyt diet, and to see how this diet might affect cancer cells in the bloodstream. This diet is experimental and is not routinely prescribed for patients with high-grade gliomas. The results of this study may be used to support larger studies investigating possible anti-tumor affects of the sHFLC + KetoPhyt diet.

Detailed Description
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This study is designed to analyze the feasibility of using the sHFLC + KetoPhyt as an anti-cancer agent against glioblastoma multiforme (GBM). While the classic ketogenic diet typically uses a 4:1 ratio of fat to proteins/carbohydrates, the sHFLC + KetoPhyt diet has a maximum 2:1 ratio. This allows increased flexibility in the diet and improved nutritional sufficiency. Preclinical and controlled patient data supports that the sHFLC + KetoPhyt diet is able to decrease blood glucose levels while increasing circulating ketones, two key effects of the ketogenic diet. As caloric restriction is not used in this approach, the investigators hypothesize that patients will be able to have an increased dietary compliance compared to those patients on the very restrictive ketogenic diet, but still achieve a ketotic state. There is general consensus in the field that the use of the phyto anti-inflammatory diet and exogenous ketone supplementation can all lead to ketosis in a matter of days, and not become what is referred to as ketone adaptative for many weeks to months. Ketosis, with blood levels of the ketone body beta-hydroxy- butarate >0.5 mM, undergoes an adaptive process where different tissues at different times alter the biochemistry of their cellular fuel sources following the switching from a glucose- to fat- and lipid-metabolism. This affects the ability to precisely measure different states of ketosis in the study population over time as the adaptive processes are temporally unique, however previous studies have described the …adaptation periods necessary… for particular tissue ketone oxidation following sustained nutritional ketosis… , and these investigators even related this to inflammation-associated cytokine expressions as the investigators propose to measure in this study.

Official Title
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A Modified Ketogenic, Anti-Inflammatory Diet for Patients With High-Grade Gliomas

Conditions
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Glioma

Intervention / Treatment
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* Dietary Supplement: Supplemental High Fat Low Carbohydrate (sHFLC) + KetoPhyt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with high-grade gliomas (World Health Organization [WHO] Grade III/IV) with newly diagnosed or recurrent disease Ability to understand and willingness to sign an informed consent form prior to any study procedures For patients treated with external beam radiation (XRT), interstitial brachytherapy or radiosurgery, an interval of > 4 weeks must have elapsed from completion of XRT to pre-registration. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia. Steroid dosing stable for at least 7 days Adequate organ function as defined by the following laboratory values: Absolute neutrophil count (ANC) ≥ 1500/mm3 Platelet Count ≥ 100,000/mm3 Creatinine ≤ 1.5 mg/dl x upper limit of normal (ULN) Creatinine Clearance ≥ 45 mL/min Total Bilirubin ≤ 1.5 x ULN (except in cases of Gilbert's disease) AST (aspartate aminotransferase)/ ALT (alanine transaminase) ≤ 2.5 x ULN Exclusion Criteria: Concurrent investigational agents or other glioma-directed therapy (chemotherapy, radiation) while on study. Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supplemental High Fat Low Carbohydrate (sHFLC) + KetoPhyt<br>Subjects will adhere to the sHFLC + KetoPhyt diet for six 4-week cycles. | Dietary Supplement: Supplemental High Fat Low Carbohydrate (sHFLC) + KetoPhyt<br>* Following a screening period, subjects will adhere to the sHFLC + KetoPhyt diet for six 4-week cycles. Patients will receive dietary advice from a Registered Dietitian (RD) to allow for the design of personalized meal plans maintaining carbohydrates up to 33% of total caloric intake, and be asked to maintain a daily dietary log. To assist patients in understanding, monitoring and controlling their dietary choices to maintain a low carbohydrate diet, they will be trained and receive assistance on the use of an online tool for tracking nutrition [Healthtrac].<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants not able to adhere the sHFLC + KetoPhyt Diet | Patients' ability to adhere to the sHFLC + KetoPhyt Diet as defined by the presence of the following: >75% compliance with taking supplement 2x/day throughout the study period >75% of days with carbohydrate intake <33% | From Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline between the patient's glucose and ketone levels at 24 weeks as assessed by the Glucose/Ketone Index (GKI) | Blood glucose and ketone levels measured at the same time once per day from baseline to 24 weeks via a glucose/ketone monitor and test strips. The Glucose/Ketone Index will be used to monitor patient's glucose and ketone levels. | Measured daily from Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days) | 
| Change from baseline in pro-inflammatory markers and exosome biomarkers at 24 weeks | Comparison of the numbers of EGFrVIII+ exosomes and exosomal microRNAs in each participant's blood measured at baseline (Cycle 1 Day 1) and 24 weeks (Cycle 6). | At Cycle 1 Day 1 and at Cycle 6 Day 1 (Each cycle is 28 days) | 
| Change from baseline between the patient's gut microbiome at 24 weeks as assessed by 16s ribosomal sequences. | DNA purified from stool samples (16s ribosomal sequences) will be compared at baseline and 24 weeks. | Measured daily from Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioma, KetoPhyt, High-grade gliomas