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

NCT02302235 | Completed Phase 2

• 1 other identifier: maesc 006
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma Multiforme of Brain

Keywords

Glioblastoma multigorme; Ketogenic Diet; radiotherapy; chemotherapy; safety; efficiency

Outcome Measures

Primary Outcomes (3)

• survival time

  We hope to achieve a substantial difference in both survival time and time to recurrence between the KD and non-KD treatment groups. Survival time of 3 years from treatment initiation and tumor progression-free time of 2.5 years from treatment initiation would be extraordinary compared to historical data.

  6 months

• time to radiological (MRI) tumor progression

  MRI outcome will be assessed by the radiographic assessment in neuro-oncology criteria based on contrast-enhanced cranial MRI scans evaluating measureable disease, measured as the sum of products of perpendicular diameters (bi-dimensional measurements) of all measurable enhancing lesions and non-measurable disease.

  6 months

• The incidence of treatment-emergent adverse events during treatment

  Incidence of treatment-emergent adverse events changes in laboratory evaluations, changes in physical examination findings will be compared between the KD and control treatment groups

  6 months

Secondary Outcomes (1)

• Tolerability of ketogenic diet: Rate of early discontinuation of subjects from the diet because of intolerability, defined as unwillingness by the subject to continue with the diet because of possible diet related side effects

  6 months

Study Arms (2)

Ketogenic Diet

ACTIVE COMPARATOR

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.

Other: Standardized Diet

Standardized diet

OTHER

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

Other: Ketogenic Diet

Interventions

Ketogenic Diet OTHER

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

Also known as: KGD

Standardized diet

Standardized Diet 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.

Ketogenic Diet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65
• Ability and willingness to signed informed consent form
• Astrocytoma grade 4 (glioblastoma multiforme, GBM, histologically confirmed, WHO criteria)
• Documented surgical resection/debulking
• Measurable contrast-enhancing GBM by MRI imaging ≤ two weeks before screening or prior to surgery if done ≤ 2 months before
• Karnovsky Performance Score of 70 or more

You may not qualify if:

• 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)
• Prior treatment with any of the following: (a) small-molecule kinase inhibitor; (b) non-cytotoxic hormonal agent; (c) KD ≤6 months of enrollment
• Planned continued use of glucocorticoids
• 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)
• 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
• History of non-glioma malignancy other than:
• Surgically excised non-melanoma skin cancer or in situ carcinoma of the cervix
• A malignancy diagnosed ≥2 years ago if the subject has had no evidence of disease for 2 years prior to screening
• History of uncontrolled hyperlipidemia
• Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements
• History of human immunodeficiency virus, or hepatitis C
• Failure to recover from \<CTCAE grade 2 toxicities related to prior therapy
• Pregnancy or breastfeeding
• Use of any investigational drug within 1 months of enrollment
• Inability or unwillingness of subject to give written informed consent

Sponsors & Collaborators

• Mid-Atlantic Epilepsy and Sleep Center, LLC: lead
• Neuroscience Research Foundation, Sewickley,PA: collaborator

Study Sites (1)

MidAtlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Related Publications (1)

• 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.

  PMID: 33292598 DERIVED

MeSH Terms

Interventions

Diet, Ketogenic

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Pavel Klein, M.D.

  Mid-Atlantic Epilepsy and Sleep Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: November 26, 2014
• Study Start: February 1, 2014
• Primary Completion: December 1, 2021
• Study Completion: May 1, 2022
• Last Updated: August 11, 2022

Record last verified: 2022-08

Locations

US (1)