Ketogenic diets as an adjuvant therapy in glioblastoma (the KEATING trial): study protocol for a randomised pilot study

BACKGROUND: Glioblastoma is the commonest form of malignant brain tumour in adults, affecting 2–3 people per 100,000 per year. Despite current treatment options including surgical resection, radiotherapy and temozolomide chemotherapy, overall survival at 2 years is approximately 27%, with a median survival of 12–14 months. The ketogenic diet (KD) is postulated to work by simulating the metabolic response to fasting by promoting the utilisation of ketones as a primary energy source, and depriving the glycolytic pathways utilised by malignant glioma cells for growth. At present, there is no consensus as to which KD is preferable, with previous case series using different KDs, at different points in the treatment pathway. The aim of this randomised pilot study is to investigate protocol feasibility, tolerability and the impact on patient health and quality of life of two different KDs within an NHS setting. The results of this pilot study will inform which KD will be most deliverable and adhered to by patients in order to test for effectiveness in future trials. METHODS: A prospective, non-blinded, randomised, pilot study will be undertaken in 12 patients with newly diagnosed glioblastoma treated by surgical resection. Patients will be randomised in a ratio of 1:1, using a permuted block randomisation method to one of two diets; the modified ketogenic diet and the medium chain triglyceride ketogenic diet. Primary data collection will take place 12 weeks after starting the diet and secondary data collection after 12 months. Feasibility will be assessed by retention and recruitment rates, ability to enrol patients prior to starting chemoradiotherapy, dietary compliance and adjustments, ketone levels, glucose levels and intervention time. Patient impact will be assessed through quality of life and food acceptability questionnaires, gastrointestinal side effects and changes to biochemical markers and anthropometric measures, assessed at regular intervals. DISCUSSION: The results of this pilot study will be used to inform the feasibility, methodological design and power calculations of future phase III clinical trials investigating the effectiveness of KD as an adjuvant therapy in the management of glioblastoma. TRIAL REGISTRATION: ISRCTN71665562 and NCT03075514.