Pilot Study of a Metabolic Nutritional Therapy for the Management of Primary Brain Tumors (Ketones)

• A CT-PET scan will be used to measure changes in brain tumor size. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Results of the metabolic therapy will be assessed by comparing CT-PET scans obtained at the beginning of the study with those after 6 and 12 weeks of metabolic therapy.
  
  

Dietary Supplement: Energy restricted Ketogenic Diet (ERKD) (Metabolic Nutritional Therapy)
Two adult subjects with reoccurring glioblastoma will be referred to the study. Residual tumor size and baseline glucose uptake will be determined by 18fluoro-deoxyglucose (18FDG) PET/CT. Subjects will then be placed on ERKD for 6 weeks using Ketocal® or food. After 6 weeks of ERKD, tumor size and tumor glucose uptake will be determined by 18FDG PET/CT. If the tumor has decreased in size or remained the same (stable disease), the subjects will be continued on the ERKD for an additional 6 weeks. Total calories consumed by each subject will be targeted to 20 to 25 kcal/kg/day. If the tumor has decreased in size or the size has remained the same then subjects will be continued on the ERKD for as additional 6 weeks. After completing 12 weeks of therapy with ERKD, patients will be reevaluated with 18FDG PET/CT. The inability of tumors to metabolize ketones is expected to prevent or slow tumor growth as evidenced by 18FDG PET/CT.
Other Name: Ketocal (Nutricia)

Summary: The current standard of care for glioblastoma multiforme (GBM), the most common primary brain tumor in adults, includes surgical resection, radiation and chemotherapy. Survival rarely exceeds 18 months. The investigators propose to test the hypothesis that brain tumor cells are unable to utilize ketones as a source of energy when deprived of glucose, due to mitochondrial dysfunction, whereas normal glia and neurons can survive this metabolic stress. A nutritionally adequate but energy restricted, ketogenic diet (ERKD) to deprive brain tumors of energy and resulting in death of glioma cells is promising. ERKD-based therapy to manage brain cancer is both biologically plausible and supported by data in animal models. A multidisciplinary team of oncologists, registered dietitians, and physiologists will implement an ERKD therapy in two (2) GBM subjects for an 8 week, phase 1 clinical trial. After receiving standard medical care for GBM including biopsy or tumor excision, ERKD therapy will be initiated for subjects during a one week inpatient admission to Sparrow Hospital and supervised by registered dietitians experienced in implementing this therapy. The objective of this trial is to determine whether the ERKD causes altered glucose metabolism in gliomas and decreases tumor size in individuals with GBM as measured by positron emission tomography/ computed tomography in the Department of Radiology at MSU. Enzymes and signaling pathways that regulate metabolism and cell growth will be assessed in initial and post-ERKD tumors using standard biochemical approaches.