Ketogenic Diet as Adjunctive Treatment in Refractory/End-stage Glioblastoma Multiforme: a Pilot Study

NCT01865162 | Completed Phase 1

• 1 other identifier: maes 002
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The first weekly KD meal package will be given to the patient at the study site. The patient will be instructed in how to process the week-long meal plan package content. Participants will measure urine ketone bodies with Ketostix 2x day and blood for glucose and ketone levels using self-administered Precision Xtra® Meter (Abbot Diabetes Care, Alameda, CA, USA) starting with the first day of the diet. Self-administered blood checks for glucose and ketone bodies will be done in fasted state in the morning and 2 hours post-prandially in the evening. Participants will be seen on day 7 of treatment by the study nutritionist and a study investigator-physician (separately) to review possible AEs, and for further education about the diet. Study staff will review and evaluate the participant's method of urine ketone and blood glucose and ketone levels testing. Subsequently, participants will be seen at one, 2 weeks, and 4 weeks after KG diet initiation, and then monthly. KD treatment will last until exit criteria are met or for 6 months, whichever comes first. Exit criteria are the primary outcome measures, the first of either (a) cerebral edema requiring steroid rescue therapy or (b) death. Treatment will occur in outpatient office setting at the Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD. The location of subsequent treatment administration may change to hospital setting at Holy Cross Hospital should a patient need hospitalization during the study for any reason, as determined by the patient's clinical care needs.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma multiforme, ketogenic diet, neoplasm

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme.

  Early treatment discontinuation, treatment compliance, 7-point Licker hunger scale, fasting lipid levels and fasting serum glucose and insulin levels

  one year

Secondary Outcomes (2)

• To obtain pilot data on efficacy of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme

  one year

• To evaluate tolerability of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme.

  one year

Study Arms (1)

ketogenic diet

EXPERIMENTAL

Treatment will consist of ketogenic diet. KD will consist of 4:1 \[fat\] : \[protein+carbohydrate\] weight ratio with 1600 kcal restriction. The diet will be supplemented with vitamins, calcium, phosphorus, zinc and selenium supplements to meet the requirements of US Dietary Reference Intakes (DRI) standard.

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. The diet will be supplemented with vitamins, calcium, phosphorus, zinc and selenium supplements to meet the requirements of US Dietary Reference Intakes (DRI) standard.

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 recurrence or progression after surgical resection/debulking, radiation and temozolamide chemotherapy.
• Measurable contrast-enhancing progressive or recurrent GBM by MRI imaging ≤ two weeks before screening.
• (a) ≥ 3months after completion of radiation; (b) 6 weeks from a nitrosourea chemotherapy; (c) ≥ weeks from a non-nitrosourea chemotherapy (all \[a-c\] in order to allow recovery from the potential of severe toxicity related to these treatments)
• 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
• University of Pittsburgh Medical Center: 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

Conditions

Glioblastoma; Neoplasms

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

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.

  Director Mid-Atlantic Epilepsy and Sleep Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2013
• First Posted: May 30, 2013
• Study Start: January 1, 2013
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: November 9, 2022

Record last verified: 2022-11

Locations

US (1)