Clinical trial NCT05373381: The KetoGlioma (Ketogenic Glioma) Study
Official title: A Modified Ketogenic, Anti-Inflammatory Diet for Patients With High-Grade Gliomas
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Glioma
Keywords: Glioma
KetoPhyt
High-grade gliomas
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
First posted: 2022-05-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants not able to adhere the sHFLC + KetoPhyt Diet
timeFrame: From Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days)
Secondary outcomes:
measure: Change from baseline between the patient's glucose and ketone levels at 24 weeks as assessed by the Glucose/Ketone Index (GKI)
timeFrame: Measured daily from Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days)
measure: Change from baseline in pro-inflammatory markers and exosome biomarkers at 24 weeks
timeFrame: At Cycle 1 Day 1 and at Cycle 6 Day 1 (Each cycle is 28 days)
measure: Change from baseline between the patient's gut microbiome at 24 weeks as assessed by 16s ribosomal sequences.
timeFrame: Measured daily from Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
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