Clinical trial NCT02286167: Glioma Modified Atkins-based Diet in Patients With Glioblastoma
Official title: The Feasibility and Biologic Effect of a Modified Atkins-based Intermittent Fasting Diet in Patients With Glioblastoma (GBM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glioblastoma Multiforme
Keywords: modified-Atkins diet
ketogenic diet
central nervous system malignancy
glioma
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
First posted: 2014-11-07
Enrollment: 25
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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Karnofsky performance status \>/= 60.
3. Patients must be at least 18 years of age.
4. 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).
5. 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:

1. 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.
2. Severe acute infection.
3. BMI \> 35.0 or BMI \< 20.0.
4. Active bowel obstruction, ileus, or active or remote pancreatitis.
5. Clinically significant heart failure (NYHA \>2), recent myocardial infarction, or symptomatic atrial fibrillation.
6. Clinically significant renal disease (creatinine \>2.0 mg/dL, urea \>100 mg/dL).
7. Clinically significant hepatic dysfunction (alanine or aspartate aminotransferase \>7 times the upper limit of normal).
8. Patients with insulin-dependent diabetes mellitus.
9. Conditions that may increase the risk of the diet or significantly reduce compliance (i.e. cognitive impairment, frank dementia, etc).
10. Other concurrent experimental therapies.
11. Milk allergy.
12. Treatment with the modified Atkins diet (MAD) for any cause within the 9 months prior to study enrollment
13. Patient inability to complete baseline screening 3-day diet record.

Primary outcomes:
measure: 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
timeFrame: 8 weeks per patient
Secondary outcomes:
measure: Biologic activity measured by pre- and post-study cerebral glutamate and glutamine concentrations assessed by MRS.
timeFrame: 8 weeks per patient
measure: Tolerability assessed by percent of patients who have an adverse reaction of any grade attributed to the diet of possible, probable, or definite
timeFrame: 8 weeks per patient
measure: Dietary Activity
timeFrame: 8 weeks per patient
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Roy E. Strowd, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Jaishri O. Blakeley, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.