Glioblastoma Multiforme
Conditions
Keywords
modified-Atkins diet, ketogenic diet, central nervous system malignancy, glioma
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.
Interventions
OTHERDiet modification
All patients will be participate in the intermittent, modified Atkins diet
Sponsors
Wake Forest University Health Sciences
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 8 weeks per patient | 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
| Measure | Time frame | Description |
|---|---|---|
| Biologic activity measured by pre- and post-study cerebral glutamate and glutamine concentrations assessed by MRS. | 8 weeks per patient | 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 | 8 weeks per patient | Percent of patients who have an adverse reaction of any grade attributed to the diet of possible, probable, or definite |
| Dietary Activity | 8 weeks per patient | Dietary compliance will be assessed by serial changes in serum glucose, ketones, weight trajectory, body fat composition, change in seizure frequency without AED adjustment |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRoy E. Strowd, MD
Wake Forest University Health Sciences
PRINCIPAL_INVESTIGATORJaishri O. Blakeley, MD
Johns Hopkins University
Outcome results
None listed