Condition category
Cancer
Date applied
13/03/2017
Date assigned
13/03/2017
Last edited
15/09/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Ms Kirsty Martin

ORCID ID

Contact details

The Walton Centre NHS Foundation Trust
University of Liverpool
Lower Lane
Liverpool
L9 7LJ
United Kingdom
+44 151 529 5593
kirsty.martin@liverpool.ac.uk

Type

Scientific

Additional contact

Mr Michael Jenkinson

ORCID ID

Contact details

The Walton Centre NHS Foundation Trust
University of Liverpool
Lower Lane
Liverpool
L9 7LJ
United Kingdom
+44 151 529 5683
michael.jenkinson@liverpool.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

33354

Study information

Scientific title

Ketogenic diets as an Adjuvant Therapy In Glioblastoma: A Randomised Pilot Study

Acronym

KEATING

Study hypothesis

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

Ethics approval

North West, Greater Manchester West Research Ethics Committee, 13/01/2017, ref: 17/NW/0013

Study design

Randomised; Interventional; Design type: Treatment, Dietary

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Brain Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of eye, brain and other parts of central nervous system

Intervention

From 31/08/2017:
Two types of ketogenic diets will be compared: the Modified Ketogenic Diet (MKD) and the Medium Chain Triglyceride (MCT) Ketogenic Diet. Patients will be randomly assigned to a diet via a permuted block randomisation method.
Both diets are high in fat and low in carbohydrates, but contain different types and amounts of fat. The MKD is 80% fat (predominantly long chain fatty acids) and 5% carbohydrate, whilst the MCT diet is 75% fat (30% of which is from medium chain fatty acids) and 10% carbohydrate. The MCT fats in this case are to be consumed through the inclusion of a nutritional supplement/ drink (Betaquik, Vitaflo International Ltd). Both diets will be calculated and supervised by a dietitian.
Patients will commence the diet up to four months post surgical resection or biopsy, prior to receiving/ whilst receiving/ after receiving oncological treatments (radiotherapy, chemotherapy or chemoradiotherapy) and follow the diet for 3 months initially (primary completion). After this period if they wish to continue with the diet follow up will be offered for 12 months (secondary completion).

Before 31/08/2017:
Two types of ketogenic diets will be compared: the Modified Ketogenic Diet (MKD) and the Medium Chain Triglyceride (MCT) Ketogenic Diet. Patients will be randomly assigned to a diet via a permuted block randomisation method.
Both diets are high in fat and low in carbohydrates, but contain different types and amounts of fat. The MKD is 80% fat (predominantly long chain fatty acids) and 5% carbohydrate, whilst the MCT diet is 75% fat (30% of which is from medium chain fatty acids) and 10% carbohydrate. The MCT fats in this case are to be consumed through the inclusion of a nutritional supplement/ drink (Betaquik, Vitaflo International Ltd). Both diets will be calculated and supervised by a dietitian.
Patients will commence the diet post surgery, prior to commencing chemo/radiotherapy and follow the diet for 3 months initially (primary completion). After this period if they wish to continue with the diet follow up will be offered for 12 months (secondary completion).

Intervention type

Other

Phase

Drug names

Primary outcome measures

Retention rate is measured by recording:
1. The number of patients who start randomized treatment as a proportion of the number randomized a 12 weeks
2. The number of patients who complete 12 months as a proportion of the number randomized
3. The time to dietary discontinuation
4. A description of barriers and facilitators to data collection and participant retention

Secondary outcome measures

From 31/08/2017:

1. Recruitment rate is assessed by actual recruitment compared to proposed recruitment at 12 months
2.1 Enrolment of patients (consent, randomisation, baseline screening) prior to receiving oncological treatment(s) is assessed by number of patients initiated on diet prior to starting oncological treatment at 12 months
2.2 Enrolment of patients (consent, randomisation, baseline screening) whilst receiving oncological treatment(s) is assessed by number of patients initiated on diet whilst receiving oncological treatment at 12 months
Enrolment of patients (consent, randomisation, baseline screening) after receiving oncological treatment(s) is assessed by number of patients initiated on diet after completing oncological treatment at 12 months
3. Long term retention is assessed by time to dietary discontinuation after week 12
4. Dietary adjustments required to achieve ketosis is assessed by number of dietary adjustments to macronutrient composition of MCT and MKD diets required to achieve ketosis at 12 months
5. Dietary compliance is assessed by a self reported by compliance rate at 2 years and Analysed by comparing macronutrient content assessed via 3 day food diaries to advised macronutrient content at 12 months
6. MCT supplement compliance is assessed by dose of MCT taken compared to dose advised at 12 months
7. Ketosis levels are assessed by self reported urinary ketone levels twice daily for first 6 weeks then once per week thereafter and blood ketone and glucose levels weekly at 12 months
8. Dietetic time required for each intervention is assessed by dietetic time spent on clinical and non clinical activities relating to the trial at 12 months
9. Protocol refinements required are assessed by number of deviations from the protocol including reasons for deviations at 12 months
10. Data to inform sample size calculations of future trials is assessed by retention rates at 12 months
11. Completeness of data for all trial outcomes is assessed by number of complete data sets for all trial outcomes at 12 months

Patient impact objectives
1. Quality of life is assessed by change in quality of life assessed through EORTC QLQ C30 and BN 20 questionnaires at baseline and 12 months
2. Food acceptability is assessed by change in food acceptability assessed through food acceptability questionnaire at baseline and 12 months
3. Gastrointestinal side effects are assessed by number of reported gastrointestinal side effects assessed through EORTC QLQ C30 questionnaire and Common Terminology Criteria for Adverse Events at baseline and 12 months
4. Changes in biochemical markers are assessed by changes to biochemical markers (renal, bone, LFT, lipid profiles) during the duration of the diet at baseline and 12 months
5. Anthropometric changes are assessed by changes to anthropometry (weight, body mass index, fat mass, muscle circumference, hand grip strength) at baseline and 12 months

Before 31/08/2017:

1. Recruitment rate is assessed by actual recruitment compared to proposed recruitment at 12 months
2. Enrolment of patients (consent, randomisation, baseline screening) pre-chemoradiation is assessed by number of patients initiated on diet prior to starting chemoradiation treatment at 12 months
3. Long term retention is assessed by time to dietary discontinuation after week 12
4. Dietary adjustments required to achieve ketosis is assessed by number of dietary adjustments to macronutrient composition of MCT and MKD diets required to achieve ketosis at 12 months
5. Dietary compliance is assessed by a self reported by compliance rate at 2 years and Analysed by comparing macronutrient content assessed via 3 day food diaries to advised macronutrient content at 12 months
6. MCT supplement compliance is assessed by dose of MCT taken compared to dose advised at 12 months
7. Ketosis levels are assessed by self reported urinary ketone levels twice daily for first 6 weeks then once per week thereafter and blood ketone and glucose levels weekly at 12 months
8. Dietetic time required for each intervention is assessed by dietetic time spent on clinical and non clinical activities relating to the trial at 12 months
9. Protocol refinements required are assessed by number of deviations from the protocol including reasons for deviations at 12 months
10. Data to inform sample size calculations of future trials is assessed by retention rates at 12 months
11. Completeness of data for all trial outcomes is assessed by number of complete data sets for all trial outcomes at 12 months

Patient impact objectives
1. Quality of life is assessed by change in quality of life assessed through EORTC QLQ C30 and BN 20 questionnaires at baseline and 12 months
2. Food acceptability is assessed by change in food acceptability assessed through food acceptability questionnaire at baseline and 12 months
3. Gastrointestinal side effects are assessed by number of reported gastrointestinal side effects assessed through EORTC QLQ C30 questionnaire and Common Terminology Criteria for Adverse Events at baseline and 12 months
4. Changes in biochemical markers are assessed by changes to biochemical markers (renal, bone, LFT, lipid profiles) during the duration of the diet at baseline and 12 months
5. Anthropometric changes are assessed by changes to anthropometry (weight, body mass index, fat mass, muscle circumference, hand grip strength) at baseline and 12 months

Overall trial start date

01/07/2016

Overall trial end date

30/06/2019

Reason abandoned

Eligibility

Participant inclusion criteria

From 31/08/2017:
1. Age 16 years and over
2. Patient at The Walton Centre NHS Foundation Trust
3. Performance status ≤2 (Sǿrensen et al., 1993)
4. Confirmed histological diagnosis of GB (WHO grade IV)
5. Undergone surgical resection or biopsy within the last 4 months and will go onto receive/ is currently receiving/ has received oncological treatment

Before 31/08/2017:
1. Age 16 years and over
2. Patient at The Walton Centre NHS Foundation Trust
3. Performance status ≤2 (Sǿrensen et al., 1993)
4. Confirmed histological diagnosis of GB (WHO grade IV)
5. Undergone surgical resection and will go onto receive chemoradiotherapy

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 12; UK Sample Size: 12

Participant exclusion criteria

From 31/08/2017:
1. Having prior use of a ketogenic diet
2. Kidney dysfunction
3. Liver dysfunction
4. Gall bladder dysfunction
5. Metabolic disorder
6. Eating disorder
7. Diabetes (requiring medication)
8. Body mass index (BMI) ≤18.5kg/m2
9. Weight loss medications
10. Currently pregnant or breastfeeding
11. Performance status ≥3

Before 31/08/2017:
1. Having prior use of a ketogenic diet
2. Kidney dysfunction
3. Liver dysfunction
4. Gall bladder dysfunction
5. Metabolic disorder
6. Eating disorder
7. Diabetes (requiring medication)
8. Body mass index (BMI) ≤18.5kg/m2
9. Weight loss medications
10. Pregnancy
11. Performance status ≥3

Recruitment start date

01/04/2017

Recruitment end date

31/03/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Walton Centre NHS Foundation Trust
Lower Lane
Liverpool
L9 7LJ
United Kingdom

Sponsor information

Organisation

University of Liverpool

Sponsor details

Research Support Office
2nd Floor Block D Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
+44 151 794 8739
sponsor@liv.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Vitaflo (International) Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The trial will be undertaken as part of a PhD programme at the University of Liverpool. Completion of a thesis is proposed for July 2019.

Results of the trial will be published as soon as possible, in an appropriate peer reviewed journal and presented at appropriate conferences. The financial sponsor Vitaflo International Ltd will be acknowledged, however they will have no part in conducting or analysing the trial.

A newsletter detailing the findings of the trial will be circulated to patients.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/12/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

15/09/2017: Internal review. 31/08/2017: Interventions, outcomes, inclusion and exclusion criteria have been modified. 06/06/2017: Internal review