Clinical trial NCT03075514: Ketogenic Diets as an Adjuvant Therapy in Glioblastoma
Official title: Ketogenic Diets as an Adjuvant Therapy in Glioblastoma: A Randomised Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glioblastoma
Glioblastoma Multiforme
Glioblastoma, Adult
Keywords: ketogenic
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: Walton Centre NHS Foundation Trust
name: Vitaflo International, Ltd
First posted: 2017-03-09
Enrollment: 12
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: MKD and MCT ketogenic diets
Primary purpose: TREATMENT

Brief summary: Glioblastoma (GB) is the commonest form of brain cancer in adults. Despite current treatment options including surgery, radiotherapy and chemotherapy, overall survival is poor. Therefore, other treatment options are being explored and there is increasing interest in the possibility of using the ketogenic diet (KD), alongside current treatment options.

The KD is a high fat, low carbohydrate diet. This encourages the body to use fat (broken down to ketones) as its primary energy source, instead of carbohydrate (broken down to glucose, a type of sugar). KDs have been considered for use in patients with GB as this type of cancer is thought to use glucose as its main energy supply, which is of short supply in this diet. Animal studies have shown KDs may make GB more responsive to radiotherapy and chemotherapy and could improve survival by slowing the cancer's growth. However, clinical studies are needed in humans to assess any possible benefits.

This trial will see patients randomly assigned to one of two types of KDs; the modified ketogenic diet (MKD) and the medium chain triglyceride ketogenic diet (MCT). Both diets follow the same high fat, low carbohydrate principles, with the MCT diet requiring the patient to take some of the fat as a supplement drink instead of as food. Patients will follow the diet for 12 weeks initially. The trial will look to enroll newly diagnosed GB patients, from The Walton Centre NHS Foundation Trust over a 12 month period.

The aim of the trial is to investigate protocol feasibility and patient impact by comparing two KDs in an NHS setting, with a view to informing future phase III clinical trials.

Detailed description: A prospective, non-blinded, randomized, pilot study will be undertaken in patients with glioblastoma (GB). Patients will be randomized to the modified ketogenic diet (MKD) or the medium chain triglyceride ketogenic diet (MCT) for a 12 week period (primary completion). If patients wish to remain on diet, they will be offered dietetic support for a total of 12 months (secondary completion).

The trial will be open to all Walton Centre Foundation Trust patients with a newly diagnosed GB, who have undergone surgical resection or biopsy within the last four months and who are going on to receive/ are currently receiving/ have completed oncological treatments (radiotherapy or chemotherapy or chemoradiotherapy). Patients will be referred via neuro-oncology multi-disciplinary meetings and neurosurgical clinics, post histology. The diet will be offered alongside standard care, commencing within four months of surgery.

Both diets are high in fat and low in carbohydrate, but contain different types and amounts of fats. The MKD is 80% fat (predominately long chain fatty acids) and 5% carbohydrate, whilst the MCT diet is 75% fat (30% of which is medium chain fatty acids) and 10% carbohydrate.

A permuted block randomization method will be adopted, using 'sealedenvelope' randomization system. This will be set up and administered by the statistician, who is not involved with the recruiting of patients.

Patients will receive regular input from the trial dietitian. This includes clinical consultations at baseline, dietary initiation, week 6, week 12 and every 3 months thereafter and telephone consultations at weeks 1, 3 and 9. Patients will receive dietary and ketone monitoring education.

Assessments and monitoring undertaken at each consultation include anthropometry, biochemistry, compliance, tolerance, acceptability, quality of life and ketosis.

Informed consent will be obtained prior to enrollment and the patient may withdraw at any time.

An information study is also embedded into KEATING, to aid understanding of the patients' recruitment experience and viewpoints, by interviewing a sub-sample of patients and their relatives/ carers. This will enable the design of bespoke strategies to optimise recruitment to future trials related to ketogenic diets and gliomas

Eligibility criteria: Inclusion Criteria:

* Age ≥16 years
* Patient at The Walton Centre NHS Foundation Trust
* Performance status ≤2
* Confirmed histological diagnosis of glioblastoma
* Undergone surgical resection or biopsy and will go onto receive/ is receiving/ has received oncological treatments

Exclusion Criteria:

* Having prior use of KD
* Kidney dysfunction
* Liver dysfunction
* Gall bladder dysfunction
* Metabolic disorder
* Eating disorder
* Diabetes (requiring medication)
* Body mass index ≤ 18.5kg/m2
* Weight loss medications
* Currently pregnant or breast feeding
* Performance status ≥3

Primary outcomes:
measure: To assess retention and drop out rates
timeFrame: 12 weeks
measure: To assess retention and drop out rates
timeFrame: 12 weeks
measure: To assess retention and drop out rates
timeFrame: 12 weeks
measure: To assess retention and drop out rates
timeFrame: 12 weeks
Secondary outcomes:
measure: Estimation of recruitment rates
timeFrame: 12 months
measure: Enrollment of patients
timeFrame: 12 months
measure: Enrollment of patients
timeFrame: 12 months
measure: Enrollment of patients
timeFrame: 12 months
measure: Long term retention
timeFrame: 2 years
measure: Dietary adjustments required to achieve ketosis
timeFrame: 2 years
measure: Self reported dietary compliance
timeFrame: 2 years
measure: Calculated dietary compliance
timeFrame: 2 years
measure: MCT compliance
timeFrame: 2 years
measure: Ketosis levels
timeFrame: 2 years
measure: Dietetic time required for interventions
timeFrame: 2 years
measure: Protocol refinements required
timeFrame: 2 years
measure: Sample size estimates for future trials
timeFrame: 2 years
measure: Quality of life
timeFrame: 2 years
measure: Food acceptability
timeFrame: 2 years
measure: Gastrointestinal side effects
timeFrame: 2 years
measure: Changes to biochemical markers
timeFrame: 2 years
measure: Anthropometric changes
timeFrame: 2 years
measure: Completeness of data
timeFrame: 2 years
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Univeristy of Liverpool/ The Walton Centre NHS Foundation Trust
state: Merseyside
Study officials:
affiliation: University of Liverpool
name: Michael D Jenkinson, PhD, FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martin-McGill KJ, Marson AG, Tudur Smith C, Jenkinson MD. Ketogenic diets as an adjuvant therapy in glioblastoma (the KEATING trial): study protocol for a randomised pilot study. Pilot Feasibility Stud. 2017 Nov 28;3:67. doi: 10.1186/s40814-017-0209-9. eCollection 2017.