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Glioma Modified Atkins-based Diet in Patients With Glioblastoma (GLAD)

Primary Purpose

Glioblastoma Multiforme

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Diet modification

About this trial

This is an interventional other trial for Glioblastoma Multiforme focused on measuring modified-Atkins diet, ketogenic diet, central nervous system malignancy, glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have a clinical and histopathologic diagnosis of GBM, have completed >80% of prescribed concurrent radiation therapy and adjuvant temozolomide without CTCEA grade 3 or 4 toxicity, and be greater than 7 months from the time of completion of concurrent chemoradiotherapy.
Karnofsky performance status >/= 60.
Patients must be at least 18 years of age.
Patients must be eligible to undergo a ketogenic or Atkins based diet according to baseline body mass index (BMI, see exclusion criteria), comorbid medical conditions (see exclusion criteria), and baseline laboratory assessment (see exclusion criteria).
Patients must be of appropriate mental capacities with sufficient social support so as to be able to complete required study activities (i.e. diet record, etc) and able to provide written informed consent.

Exclusion Criteria:

Patients with a history of a metabolic disorder including documented defect in urea metabolism (including documented history of gout), carnitine deficiency (primary carnitine deficiency, carnitine palmitoyltransferase I or II deficiency, carnitine translocase deficiency), fatty acid metabolism, beta-oxidation defects, pyruvate carboxylase deficiency, mitochondrial function, porphyria, or nephrolithiasis.
Severe acute infection.
BMI > 35.0 or BMI < 20.0.
Active bowel obstruction, ileus, or active or remote pancreatitis.
Clinically significant heart failure (NYHA >2), recent myocardial infarction, or symptomatic atrial fibrillation.
Clinically significant renal disease (creatinine >2.0 mg/dL, urea >100 mg/dL).
Clinically significant hepatic dysfunction (alanine or aspartate aminotransferase >7 times the upper limit of normal).
Patients with insulin-dependent diabetes mellitus.
Conditions that may increase the risk of the diet or significantly reduce compliance (i.e. cognitive impairment, frank dementia, etc).
Other concurrent experimental therapies.
Milk allergy.
Treatment with the modified Atkins diet (MAD) for any cause within the 9 months prior to study enrollment
Patient inability to complete baseline screening 3-day diet record.

Sites / Locations

The Johns Hopkins Hospital
Wake Forest School of Medicine

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Single arm diet

Arm Description

Intermittent, modified Atkins diet

Outcomes

Primary Outcome Measures

Feasibility of intermittent modified Atkins diet in patients with GBM assessed by percent of patients able to remain on the diet and achieve nutritional goals

Percent of patients able to remain on the diet and achieve nutritional goals as defined by cumulative assessment of diet records collected at weeks 4, 6, and 8 with a 60% completion defined as a positive results

Secondary Outcome Measures

Biologic activity measured by pre- and post-study cerebral glutamate and glutamine concentrations assessed by MRS.

Measured by pre- and post-study cerebral glutamate and glutamine concentrations assessed by MRS.

Tolerability assessed by percent of patients who have an adverse reaction of any grade attributed to the diet of possible, probable, or definite

Percent of patients who have an adverse reaction of any grade attributed to the diet of possible, probable, or definite

Dietary Activity

Dietary compliance will be assessed by serial changes in serum glucose, ketones, weight trajectory, body fat composition, change in seizure frequency without AED adjustment

Full Information

NCT ID

NCT02286167

First Posted

November 5, 2014

Last Updated

May 8, 2020

Sponsor

Wake Forest University Health Sciences

Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

1. Study Identification

Unique Protocol Identification Number

NCT02286167

Brief Title

Glioma Modified Atkins-based Diet in Patients With Glioblastoma

Acronym

GLAD

Official Title

The Feasibility and Biologic Effect of a Modified Atkins-based Intermittent Fasting Diet in Patients With Glioblastoma (GBM)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

November 2014 (Actual)

Primary Completion Date

January 3, 2019 (Actual)

Study Completion Date

July 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary goal of this study is to assess the feasibility and biologic activity of a modified Atkins-based diet combined with short-term intermittent fasting, a GLioma Atkins-based Diet (GLAD), in patients with central nervous system GBM.

Detailed Description

Malignant gliomas have a high glycolytic rate and are dependent on glucose for energy metabolism. This so called "Warburg effect" or the reliance of central nervous system (CNS) tumor cells on glucose utilization through glycolysis has been identified as a potential therapeutic target in cancer metabolism. Preclinically, reduced cerebral glucose via calorie restriction has been repeatedly associated with tumor reduction and improved survival in glioma animal models. Such work has led to several early clinical studies evaluating the ketogenic diet (KD) in patients with recurrent GBM. The modified Atkins diet (MAD) is designed to provide a more palatable, less restrictive but effective alternative to the strict KD, particularly for adults. The MAD does not require inpatient admission for initial fast, weight of foods, or severe dietary restrictions and is generally well tolerated, easier to administer, and more practical for adults. The MAD lacks calorie restriction, an important component to dietary therapies in preclinical investigations. Emerging evidence also suggests that short term fasting may provide superior anti-cancer activity to long term calorie restriction and that these benefits have been observed without substantial weight loss that can be observed with longer term calorie restriction. In glioma patients, a diet therapy that combines the broad clinical application of the MAD with the caloric impact of short-term intermittent fasting is therefore optimal. Moreover, initiation of this diet when the cancer has already undergone induction therapy and is clinically and radiographically stable, may provide the optimal time for metabolic intervention to prevent recurrence or progression.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

modified-Atkins diet, ketogenic diet, central nervous system malignancy, glioma

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single arm diet

Arm Type

Other

Arm Description

Intermittent, modified Atkins diet

Intervention Type

Other

Intervention Name(s)

Diet modification

Intervention Description

All patients will be participate in the intermittent, modified Atkins diet

Primary Outcome Measure Information:

Title

Feasibility of intermittent modified Atkins diet in patients with GBM assessed by percent of patients able to remain on the diet and achieve nutritional goals

Description

Time Frame

8 weeks per patient

Secondary Outcome Measure Information:

Title

Biologic activity measured by pre- and post-study cerebral glutamate and glutamine concentrations assessed by MRS.

Description

Measured by pre- and post-study cerebral glutamate and glutamine concentrations assessed by MRS.

Time Frame

8 weeks per patient

Title

Tolerability assessed by percent of patients who have an adverse reaction of any grade attributed to the diet of possible, probable, or definite

Description

Percent of patients who have an adverse reaction of any grade attributed to the diet of possible, probable, or definite

Time Frame

8 weeks per patient

Title

Dietary Activity

Description

Dietary compliance will be assessed by serial changes in serum glucose, ketones, weight trajectory, body fat composition, change in seizure frequency without AED adjustment

Time Frame

8 weeks per patient

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have a clinical and histopathologic diagnosis of GBM, have completed >80% of prescribed concurrent radiation therapy and adjuvant temozolomide without CTCEA grade 3 or 4 toxicity, and be greater than 7 months from the time of completion of concurrent chemoradiotherapy. Karnofsky performance status >/= 60. Patients must be at least 18 years of age. Patients must be eligible to undergo a ketogenic or Atkins based diet according to baseline body mass index (BMI, see exclusion criteria), comorbid medical conditions (see exclusion criteria), and baseline laboratory assessment (see exclusion criteria). Patients must be of appropriate mental capacities with sufficient social support so as to be able to complete required study activities (i.e. diet record, etc) and able to provide written informed consent. Exclusion Criteria: Patients with a history of a metabolic disorder including documented defect in urea metabolism (including documented history of gout), carnitine deficiency (primary carnitine deficiency, carnitine palmitoyltransferase I or II deficiency, carnitine translocase deficiency), fatty acid metabolism, beta-oxidation defects, pyruvate carboxylase deficiency, mitochondrial function, porphyria, or nephrolithiasis. Severe acute infection. BMI > 35.0 or BMI < 20.0. Active bowel obstruction, ileus, or active or remote pancreatitis. Clinically significant heart failure (NYHA >2), recent myocardial infarction, or symptomatic atrial fibrillation. Clinically significant renal disease (creatinine >2.0 mg/dL, urea >100 mg/dL). Clinically significant hepatic dysfunction (alanine or aspartate aminotransferase >7 times the upper limit of normal). Patients with insulin-dependent diabetes mellitus. Conditions that may increase the risk of the diet or significantly reduce compliance (i.e. cognitive impairment, frank dementia, etc). Other concurrent experimental therapies. Milk allergy. Treatment with the modified Atkins diet (MAD) for any cause within the 9 months prior to study enrollment Patient inability to complete baseline screening 3-day diet record.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roy E. Strowd, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jaishri O. Blakeley, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Johns Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Wake Forest School of Medicine

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34233941

Citation

Schreck KC, Hsu FC, Berrington A, Henry-Barron B, Vizthum D, Blair L, Kossoff EH, Easter L, Whitlow CT, Barker PB, Cervenka MC, Blakeley JO, Strowd RE. Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma. Neurology. 2021 Aug 31;97(9):e953-e963. doi: 10.1212/WNL.0000000000012386. Epub 2021 Jul 7.

Results Reference

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Glioma Modified Atkins-based Diet in Patients With Glioblastoma

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