Keto-Brain:Investigating the Use of Ketogenic Diets in Brain Metastases

Keto-Brain: Investigating the Use of Ketogenic Diets in Brain Metastases

This pilot study will be a single center, randomized controlled study of 24 participants with diagnosed BM (various primary disease sites) comparing the effect of a ketogenic (n=12) and AICR (n=12) diet. Potential participants will be identified via medical record reviews and chart reviews. Eligibility of patients will be assessed via medical record review. Randomization will be balanced by blocks of random sizes but no stratification due to the small sample size. Both groups will undergo a 16-week diet intervention where research dietitians will provide educations, recipes and grocery lists on the participants assigned diet. Each group will receive 4-7 days worth of food prior to testing days to both aid in transitioning to each dietary arm and to ensure that the metabolic needs for each arm are met. In an effort to maintain a patient centric focus and monitor changes in quality of life (QOL) all patients will complete psychosocial and behavioral inventories. These inventories aim to capture a holistic view on the proposed nutritional intervention during treatment. Primary outcomes will be determined at baseline, 8 weeks, and 16 weeks while patient-centric outcomes will be assessed every four weeks. Participants will have counseling by the attending physician for additional applicable medications for any treatment related side effects or toxicities. The intervention groups will undergo their randomized dietary regimen for 16 weeks.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases, Adult
• Intervention / Treatment: Other: Questionnaire Administration; Other: Laboratory Biomarker Analysis; Other: Neurocognitive Assessment; Device: Fitbit; Dietary supplement: Dietary Intervention

Detailed Description

Neurological tissues are among the most common (>10% of cancer patients) and debilitating sites for metastatic disease to develop. The brain is a 'sanctuary site' for many cancer cells and remains a challenging site to treat. Surgery and radiation therapies are the most common treatments. The investigators hypothesize that the metabolic adaptations associated with a well-formulated ketogenic diet that induces nutritional ketosis will significantly improve the response to surgery and radiation in patients with brain metastases. To date, numerous preclinical studies have demonstrated the ability of nutritional ketosis and caloric restriction to augment the therapeutic efficacy of radiotherapy. Use of a ketogenic diet is known to decrease the protein expression of HIF-1 and VEGFR2, and may increase radio sensitivity by normalizing tumor vasculature and increasing facilitated oxygen delivery to tumor cells. Several additional proposed mechanisms exist for enhancing radiosensitivity of the malignancy including: HDAC dependent mechanisms, ATP deprivation, mitochondrial ROS production and downregulation of IGF-1 receptor. Short-term fasting, a way to increase ketones acutely, has been demonstrated to speed up mitotic rates and thus facilitate a DNA damage sensitization. Lastly, a recent study showed that glucose restriction lowered Ki-67 expression, clonogenic frequency and rate of proliferation in gliomaspheres in vitro.

The investigating team team has an established expertise in conducting ketogenic diet interventions. Many individuals have adopted a low-carbohydrate diet for health reasons, yet there is scarce professional support available to provide guidance and support, especially for ketogenic diets. The investigators have scientific expertise and practical knowledge of both ketogenic and current standard of care cancer diets combined with a passion to empower people with the tools to implement these eating approaches into the participant's lifestyle. This project is highly patient-centered. The investigators will support patients who are randomized into either one of the intervention groups and provide them with a personalized eating plan designed to have maximal therapeutic impact and positively impact their lives. To that end, this project is unique in that it is highly patient-centered while also designed to have a substantial scientific and practical impact on medical management of brain metastasis treatments.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Measurable brain lesions noted on baseline MRI imaging
• Graded Prognostic Assessment > 1.5
• Body mass index (BMI) ≥18 kg/m2
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1 (0=participant has either normal activity, 1= participant has some symptoms but is nearly full ambulatory)
• Able and willing to follow prescribed diet intervention
• Scheduled to receive SRS

Exclusion Criteria:• Undergoing whole brain radiation therapy

• BMI <18 kg/m2
• Pregnant or nursing women
• Not willing to be randomized into either of the dietary interventions
• Unable to provide Informed Consent
• No previous diagnosis of small cell lung carcinoma
• No previous or suspected leptomeningeal disease
• Type 1 diabetes or insulin-dependent Type II diabetes
• Abnormal renal function (GFR < 55 mL/min, creatinine >2.0, urinary albumin >1 g/day) Not MRI eligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard of Care; Patients receive standard of care therapy with SRS and AICR Diet education.	Other: Questionnaire Administration; Ancillary studies; Other: Laboratory Biomarker Analysis; Correlative Studies; Other: Neurocognitive Assessment; NRG-CC; Device: Fitbit; Fitbit Activity Tracking
EXPERIMENTAL: Standard of Care + Ketogenic Diet; (standard of care, ketogenic diet) Patients receive standard of care with SRS. Patients undergo a controlled feeding period ketogenic diet comprising of meals for the first week and then transition into a free living with guided support type of intervention.	Other: Questionnaire Administration; Ancillary studies; Other: Laboratory Biomarker Analysis; Correlative Studies; Other: Neurocognitive Assessment; NRG-CC; Device: Fitbit; Fitbit Activity Tracking; Dietary supplement: Dietary Intervention; Undergo ketogenic diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of maintaining a ketogenic versus AICR diet in patients with brain metastasis selected for radiosurgery	Summaries from questionnaires will be plotted over time to assess adherence and compliance to the ketogenic diet.	Up to 16 weeks
Feasibility of maintaining a ketogenic diet in patients with brain metastasis selected for radiosurgery	Summaries from ketone logs will be plotted over time to assess adherence and compliance to the ketogenic diet.	Up to 16 weeks
Metabolic outcomes of a ketogenic versus AICR diet in patients with brain metastasis selected for radiosurgery	Summaries from blood markers will be plotted over time to assess adherence and compliance to the ketogenic diet.	Up to 16 weeks
Number of Participants with partial-or-complete response according to RECIST v1.1	use a Chi-squared test for the association between treatment group and partial-or-complete response according to RECIST v1.1	Baseline up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary effects of the ketogenic versus AICR diet on Neurocognitive Function Scores in BM individuals undergoing radiation therapy	same linear mixed effects model as for the primary objective, but with the following quality-of-life endpoints as outcomes	Baseline up to 16 weeks
Preliminary effects of the ketogenic versus AICR diet on PROMIS Cognitive Function Short Form 8a Scores in BM individuals undergoing radiation therapy	same linear mixed effects model as for the primary objective, but with the following quality-of-life endpoints as outcomes	Baseline up to 16 weeks
Preliminary effects of the ketogenic versus AICR diet on Heart Hope Scale in BM individuals undergoing radiation therapy to asses quality of life	same linear mixed effects model as for the primary objective, but with the following quality-of-life endpoints as outcomes	Baseline up to 16 weeks

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 26, 2022
• Primary Completion (ANTICIPATED): July 1, 2024
• Study Completion (ANTICIPATED): July 1, 2024

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (ACTUAL): June 23, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 2020C0046

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No