The KetoGlioma (Ketogenic Glioma) Study

January 31, 2024 updated by: Tufts Medical Center

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Supplemental High Fat Low Carbohydrate (sHFLC) + KetoPhyt
Subjects will adhere to the sHFLC + KetoPhyt diet for six 4-week cycles.
Dietary supplement: Supplemental High Fat Low Carbohydrate (sHFLC) + KetoPhyt
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].

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants not able to adhere the sHFLC + KetoPhyt Diet
Time Frame: From Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days)

Patients' ability to adhere to the sHFLC + KetoPhyt Diet as defined by the presence of the following:

  1. >75% compliance with taking supplement 2x/day throughout the study period
  2. >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)
Time Frame: Measured daily from Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days)
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
Time Frame: At Cycle 1 Day 1 and at Cycle 6 Day 1 (Each cycle is 28 days)
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.
Time Frame: Measured daily from Cycle 1 Day 1 to end of Cycle 6 (Each cycle is 28 days)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tufts Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2022

Primary Completion (Actual)

May 18, 2022

Study Completion (Actual)

May 18, 2022

Study Registration Dates

First Submitted

April 26, 2022

First Submitted That Met QC Criteria

May 12, 2022

First Posted (Actual)

May 13, 2022

Study Record Updates

Last Update Posted (Actual)

February 2, 2024

Last Update Submitted That Met QC Criteria

January 31, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KetoGlioma
  • STUDY00001948 (Tufts Medical Center)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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