Ketogenic Diet Treatment Adjunctive to Radiation and Chemotherapy in Glioblastoma Multiforme: a Pilot Study

NCT ID: NCT02302235

Last Updated: 2022-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2022-05-31

Brief Summary

The goal of the present study is to evaluate efficacy, safety and tolerability of 4:1 ketogenic diet administered adjunctively to standard radiation and temozolomide chemotherapy in patients with GBM in a prospective, randomized open label study.

Detailed Description

Primary aims of the study will be to 1) To evaluate efficacy of ketogenic diet as adjunctive treatment of radiation treatment in glioblastoma multiforme. 2) To evaluate the safety of ketogenic diet as adjunctive treatment of radiation treatment in glioblastoma multiforme. Secondary aim will be to evaluate tolerability of ketogenic diet as adjunctive treatment of radiation treatment in glioblastoma multiforme.

Participants will be seen at one, 2 weeks, and 4 weeks after KG diet initiation, and then monthly until month 6 after diet initiation, then every 2 months until 2 years after treatment initiation or death, then every 3 months until 3 years after treatment initiation or death. KD treatment will last for 6 months or until exit criteria are met, whichever comes first. Exit criteria are the primary outcome measures, the first of either (a) MRI tumor progression or (b) death. Secondary outcome measures will include treatment compliance, hunger scale scores, fasting serum glucose and BOH levels and occurrence of adverse events.

Patients with documented tumor progression will receive standard care for progressive GBM as directed by their treating oncologist, independent of the study.

Conditions

Glioblastoma Multiforme of Brain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ketogenic Diet

Treatment will consist of ketogenic diet. KGD will consist of 4:1 \[fat\] : \[protein+carbohydrate\] weight ratio with 1600 kcal restriction. Diet will be started at the time of initiation of radiation treatment.

Group Type: ACTIVE_COMPARATOR

Standardized Diet

Intervention Type: OTHER

Participants with GBM treated with radiation and temozolomide after surgical debulking treatment. The subjects will be taken standard diet in a 1:1 ratio. Diet will be started at the time of initiation of radiation treatment.

Standardized diet

The subjects will be taken standard diet in a 1:1 ratio.

Group Type: OTHER

Ketogenic Diet

Intervention Type: OTHER

Treatment will consist of ketogenic diet. KD will consist of 4:1 \[fat\] : \[protein+carbohydrate\] weight ratio with 1600 kcal restriction.

Interventions

Ketogenic Diet

Treatment will consist of ketogenic diet. KD will consist of 4:1 \[fat\] : \[protein+carbohydrate\] weight ratio with 1600 kcal restriction.

Intervention Type: OTHER

Standardized Diet

Participants with GBM treated with radiation and temozolomide after surgical debulking treatment. The subjects will be taken standard diet in a 1:1 ratio. Diet will be started at the time of initiation of radiation treatment.

Intervention Type: OTHER

Other Intervention Names

KGD

Eligibility Criteria

Inclusion Criteria

1. Age 18-65

2. Ability and willingness to signed informed consent form

3. Astrocytoma grade 4 (glioblastoma multiforme, GBM, histologically confirmed, WHO criteria)

4. Documented surgical resection/debulking

5. Measurable contrast-enhancing GBM by MRI imaging ≤ two weeks before screening or prior to surgery if done ≤ 2 months before

6. Karnovsky Performance Score of 70 or more

Exclusion Criteria

1. Acute intracranial or intratumoral hemorrhage > Grade 1 either by MRI or CT scan ≤2 weeks of screening. (Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study)

2. Prior treatment with any of the following: (a) small-molecule kinase inhibitor; (b) non-cytotoxic hormonal agent; (c) KD ≤6 months of enrollment

3. Planned continued use of glucocorticoids

4. Anticoagulation treatment with ≥ 1 mg/day coumadin ≤ 7 days prior to screening (low-dose [≤ 1 mg/day] coumadin, heparin, and low-molecular-weight heparin are permitted)

5. Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, unstable metabolic or endocrine disturbances, renal or liver disease, past history of renal calculi, hyperuricemia, hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism, porphyria, carnitine deficiency and pancreatitis

6. History of non-glioma malignancy other than:

1. Surgically excised non-melanoma skin cancer or in situ carcinoma of the cervix

2. A malignancy diagnosed ≥2 years ago if the subject has had no evidence of disease for 2 years prior to screening

7. History of uncontrolled hyperlipidemia

8. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements

9. History of human immunodeficiency virus, or hepatitis C

10. Failure to recover from <CTCAE grade 2 toxicities related to prior therapy

11. Pregnancy or breastfeeding

12. Use of any investigational drug within 1 months of enrollment

13. Inability or unwillingness of subject to give written informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neuroscience Research Foundation, Sewickley,PA

UNKNOWN

Sponsor Role: collaborator

Mid-Atlantic Epilepsy and Sleep Center, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pavel Klein, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mid-Atlantic Epilepsy and Sleep Center

Locations

MidAtlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Countries

United States

References

Klein P, Tyrlikova I, Zuccoli G, Tyrlik A, Maroon JC. Treatment of glioblastoma multiforme with "classic" 4:1 ketogenic diet total meal replacement. Cancer Metab. 2020 Nov 9;8(1):24. doi: 10.1186/s40170-020-00230-9.

Reference Type: DERIVED

PMID: 33292598 (View on PubMed)

Other Identifiers

maesc 006

Identifier Type: -

Identifier Source: org_study_id