Ketogenic diets as an adjuvant therapy in glioblastoma (the KEATING trial)

ISRCTN	ISRCTN71665562
DOI	https://doi.org/10.1186/ISRCTN71665562
ClinicalTrials.gov number	NCT03075514
Secondary identifying numbers	33354

Submission date: 13/03/2017
Registration date: 13/03/2017
Last edited: 14/04/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-comparing-types-of-ketogenic-diet-in-people-with-glioblastoma-keating

Contact information

Ms Kirsty Martin-McGill
Public

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

Phone	+44 (0)151 529 5593
Email	kirsty.martin@liverpool.ac.uk

Mr Michael Jenkinson
Scientific

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

Phone	+44 (0)151 529 5683
Email	michael.jenkinson@liverpool.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment, Dietary
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Ketogenic diets as an adjuvant therapy In glioblastoma: a randomised pilot study
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(s)	North West, Greater Manchester West Research Ethics Committee, 13/01/2017, ref: 17/NW/0013
Condition	Glioblastoma
Intervention	Added 04/01/2018: An information study is embedded into KEATING, with the aim of identifying recruitment challenges and aid understanding of the patients’ recruitment experience, 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. 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
Primary outcome measure	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 study start date	01/07/2016
Overall study end date	05/03/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	16 Years
Sex	Both
Target number of participants	Planned Sample Size: 12; UK Sample Size: 12
Total final enrolment	12
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 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	09/02/2018

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

The Walton Centre NHS Foundation Trust

Lower Lane
Liverpool
L9 7LJ
United Kingdom

Sponsor information

University of Liverpool
University/education

Research Support Office
2nd Floor Block D Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom

Phone	+44 (0)151 794 8739
Email	sponsor@liv.ac.uk
"ROR"	https://ror.org/04xs57h96

Funders

Funder type

Industry

Vitaflo
Private sector organisation / For-profit companies (industry)

Location: United Kingdom

Results and Publications

Intention to publish date	05/03/2020
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	28/11/2017		Yes	No
Results article	results	01/03/2020	18/03/2020	Yes	No
Plain English results			14/04/2021	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

14/04/2021: CRUK link added to Results (plain English).
18/03/2020: Publication reference added.
04/07/2019: ClinicalTrials.gov number added.
03/04/2019: The following changes have been made:
1. The final enrolment number has been added.
2. The recruitment end date has been changed from 31/03/2019 to 09/02/2018.
3. The overall trial end date has been changed from 30/06/2019 to 05/03/2019.
4. The intention to publish date has been changed from 31/12/2019 to 05/03/2020.
26/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Brain Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of eye, brain and other parts of central nervous system" to "Glioblastoma" following a request from the NIHR.
29/01/2018: Publication reference added.
16/01/2018: Cancer Help UK lay summary link added to plain English summary field.
04/01/2018: Contact and intervention clarification. recruitment dates changed from 31/03/2018 to 31/03/2019.
31/08/2017: Interventions, outcomes, inclusion and exclusion criteria have been modified.