Clinical trial NCT05428852: Keto-Brain:Investigating the Use of Ketogenic Diets in Brain Metastases
Official title: Keto-Brain: Investigating the Use of Ketogenic Diets in Brain Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Brain Metastases, Adult
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2022-06-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of maintaining a ketogenic versus AICR diet in patients with brain metastasis selected for radiosurgery
timeFrame: Up to 16 weeks
measure: Feasibility of maintaining a ketogenic diet in patients with brain metastasis selected for radiosurgery
timeFrame: Up to 16 weeks
measure: Metabolic outcomes of a ketogenic versus AICR diet in patients with brain metastasis selected for radiosurgery
timeFrame: Up to 16 weeks
measure: Number of Participants with partial-or-complete response according to RECIST v1.1
timeFrame: Baseline up to 16 weeks
Secondary outcomes:
measure: Preliminary effects of the ketogenic versus AICR diet on Neurocognitive Function Scores in BM individuals undergoing radiation therapy
timeFrame: Baseline up to 16 weeks
measure: Preliminary effects of the ketogenic versus AICR diet on PROMIS Cognitive Function Short Form 8a Scores in BM individuals undergoing radiation therapy
timeFrame: Baseline up to 16 weeks
measure: Preliminary effects of the ketogenic versus AICR diet on Heart Hope Scale in BM individuals undergoing radiation therapy to asses quality of life
timeFrame: Baseline up to 16 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Jeff Volek, PhD
role: PRINCIPAL_INVESTIGATOR
References: