Glioma Modified Atkins-based Diet in Patients With Glioblastoma

Glioblastoma Multiforme Clinical Trial

— GLAD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02286167
• Other study ID #: IRB00037347
• Status: Completed
• Phase: N/A
• Start date: November 2014
• Est. completion date: July 12, 2019

Study information

• Verified date: August 2019
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 12, 2019
• Est. primary completion date: January 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Other:
• Diet modification
All patients will be participate in the intermittent, modified Atkins diet

Locations

Country	Name	City	State
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	8 weeks per patient
Secondary	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.	8 weeks per patient
Secondary	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	8 weeks per patient
Secondary	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	8 weeks per patient