Karisa C Schreck1, Fang-Chi Hsu1, Adam Berrington1, Bobbie Henry-Barron1, Diane Vizthum1, Lindsay Blair1, Eric H Kossoff1, Linda Easter1, Christopher T Whitlow1, Peter B Barker1, Mackenzie C Cervenka1, Jaishri O Blakeley1, Roy E Strowd2. 1. From the Departments of Neurology (K.C.S., J.O.B., L.B., E.H.K., M.C.C., R.E.S.), Oncology (K.C.S., J.O.B.), Neurosurgery (K.C.S., J.O.B.), and Radiology (A.B., P.B.B.) and Institute for Clinical and Translational Research (B.H.-B., D.V.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biostatistics and Data Science (F.-C.H., C.T.W.), Clinical Research Unit (L.E.), Department of Radiology (C.T.W.), Department of Biomedical Engineering (C.T.W.), Clinical and Translational Science Institute (C.T.W.), Department of Neurology (R.E.S.), and Department of Oncology (R.E.S.), Wake Forest School of Medicine, Winston-Salem, NC; and Sir Peter Mansfield Imaging Centre (A.B.), School of Physics and Astronomy, University of Nottingham, UK. 2. From the Departments of Neurology (K.C.S., J.O.B., L.B., E.H.K., M.C.C., R.E.S.), Oncology (K.C.S., J.O.B.), Neurosurgery (K.C.S., J.O.B.), and Radiology (A.B., P.B.B.) and Institute for Clinical and Translational Research (B.H.-B., D.V.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biostatistics and Data Science (F.-C.H., C.T.W.), Clinical Research Unit (L.E.), Department of Radiology (C.T.W.), Department of Biomedical Engineering (C.T.W.), Clinical and Translational Science Institute (C.T.W.), Department of Neurology (R.E.S.), and Department of Oncology (R.E.S.), Wake Forest School of Medicine, Winston-Salem, NC; and Sir Peter Mansfield Imaging Centre (A.B.), School of Physics and Astronomy, University of Nottingham, UK. rstrowd@wakehealth.edu.
Abstract
OBJECTIVE: To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma. METHODS: Twenty-five patients with biopsy-confirmed World Health Organization grade 2 to 4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week Glioma Atkins-Based Diet (GLAD). GLAD consisted of 2 fasting days (calories <20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates ≤20 g/d) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, insulin-like growth factor-1, and magnetic resonance spectroscopy at baseline and week 8. RESULTS: Twenty-one patients (84%) completed the study. Eighty percent of patients reached ≥40 mg/dL urine acetoacetate during the study. Forty-eight percent of patients were adherent by food record. The diet was well tolerated, with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity, including hemoglobin A1c, insulin, and fat body mass, decreased significantly, while lean body mass increased. Magnetic resonance spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate [bHB] and acetone) in both lesional and contralateral brain compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB R s = 0.52, p = 0.05). Subgroup analysis of isocitrate dehydrogenase-mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria. CONCLUSION: The GLAD dietary intervention, while demanding, produced meaningful ketonuria and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02286167.
OBJECTIVE: To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma. METHODS: Twenty-five patients with biopsy-confirmed World Health Organization grade 2 to 4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week Glioma Atkins-Based Diet (GLAD). GLAD consisted of 2 fasting days (calories <20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates ≤20 g/d) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, insulin-like growth factor-1, and magnetic resonance spectroscopy at baseline and week 8. RESULTS: Twenty-one patients (84%) completed the study. Eighty percent of patients reached ≥40 mg/dL urine acetoacetate during the study. Forty-eight percent of patients were adherent by food record. The diet was well tolerated, with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity, including hemoglobin A1c, insulin, and fat body mass, decreased significantly, while lean body mass increased. Magnetic resonance spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate [bHB] and acetone) in both lesional and contralateral brain compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB R s = 0.52, p = 0.05). Subgroup analysis of isocitrate dehydrogenase-mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria. CONCLUSION: The GLAD dietary intervention, while demanding, produced meaningful ketonuria and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02286167.
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