Glioma Modified Atkins-based Diet in Patients With Glioblastoma

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.

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.