The ketogenic diet for patients with brain tumours: Two parallel randomised trials

The ketogenic diet (KD) has attracted considerable interest from the brain tumour community. There is evidence for synergy with radiotherapy in animal models, and improved seizure control in children with epilepsy due to... [ view full abstract ]

The ketogenic diet (KD) has attracted considerable interest from the brain tumour community. There is evidence for synergy with radiotherapy in animal models, and improved seizure control in children with epilepsy due to structural abnormalities. However, there is little data on mechanism or effect in brain tumour patients, and different options for implementing the ketogenic diet.

In November 2016 we assembled multiple stakeholders, including the James Lind PSP in neuro-oncology and several charities to develop a trial outline. We addressed mechanistic, clinical and practical factors to develop a trial protocol.

Based on the meeting, we are planning two parallel open-label phase 2 randomised trials of the Modified Ketogenic Diet (MKD) in patients with high grade gliomas (HGG) receiving chemoradiotherapy, and in patients with low- grade gliomas (LGG). Patients will be enrolled following a histological diagnosis and informed consent. They will receive training on a Modified Ketogenic Diet (MKD) and dietetic support throughout the trial.

Patients will be aged 18+, performance score <=2, with adequate baseline blood parameters and will not have received previous treatment (except surgery). Patients will receive standard clinical care as usual. The primary endpoint will be overall survival (not powered for comparison) (HGG) and symptom levels (LGG), with secondary endpoints including the degree and length of ketosis, disease progression and quality of life measures, including seizures. Translational assessments will include blood ketone (BHB) levels, changes in specific miRNA levels in plasma, tumour sample analysis and MRI/ MRS-based assessment of ketosis and tumour response. There is an embedded psychological component to explore patient experience, explore reasons for participation and the psychological impact of the trial.

Given the nature of the trial, we are intending to open the trial in 3 - 5 centres to concentrate dietetic support.