GlioblastomaKEATINGNCT03075514
Ketogenic Diets as an Adjuvant Therapy in Glioblastoma
A study testing MKD and MCT in people with Glioblastoma and Glioblastoma Multiforme, run by University of Liverpool at 1 site in United Kingdom.
Trial 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)… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma, Adult
- What is being tested?
- MKD and MCT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2017to 5 Mar 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Having prior use of KD
- Kidney dysfunction
- Liver dysfunction
- Gall bladder dysfunction
- Metabolic disorder
- Eating disorder
Show all 11Show fewer
- Diabetes (requiring medication)
- Body mass index ≤ 18.5kg/m2
- Weight loss medications
- Currently pregnant or breast feeding
- Performance status ≥3
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Univeristy of Liverpool/ The Walton Centre NHS Foundation Trust
Liverpool, Merseyside, L9 7LJ
About this study
Official title: Ketogenic Diets as an Adjuvant Therapy in Glioblastoma: A Randomised Pilot Trial
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.
Read more
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.
Read the 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
- Conditions
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma, Adult
- Being tested
- MKD, MCT
- Keywords
- ketogenic
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MKDOther
Modified ketogenic diet
MCTOther
Medium chain triglyceride ketogenic diet
| Study group | Role | What they receive |
|---|---|---|
| Modified ketogenic diet (MKD) | Active comparator | MKD: 80% fat and 5% carbohydrate (% of total energy requirements per day). Receives: Other: MKD |
| Medium chain triglyceride (MCT) diet | Active comparator | MCT: 75% fat (30% of which is medium chain fatty acids taken as a supplement) and 5% carbohydrate (% of total energy requirements per day). Receives: Other: MCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess retention and drop out rates
Number of patients who start randomized treatment as a proportion of the number randomized ;
Measured: 12 weeks
To assess retention and drop out rates
The number of patients who complete 12 weeks as a proportion of the number randomized
Measured: 12 weeks
To assess retention and drop out rates
Description of barriers and facilitators to data collection and participant retention
Measured: 12 weeks
To assess retention and drop out rates
The time to dietary discontinuation
Measured: 12 weeks
Secondary outcomes (19)
Estimation of recruitment rates
Actual recruitment compared to proposed recruitment
Measured: 12 months
Enrollment of patients
Number of patients initiated on diet prior to starting oncological treatments.
Measured: 12 months
Enrollment of patients
Number of patients initiated on diet during oncological treatments.
Measured: 12 months
Enrollment of patients
Number of patients initiated on diet post oncological treatments.
Measured: 12 months
Long term retention
Time to dietary discontinuation after week 12
Measured: 2 years
Dietary adjustments required to achieve ketosis
Number of dietary adjustments to macronutrient composition of MCT and MKD diets required to achieve ketosis.
Measured: 2 years
Self reported dietary compliance
Self reported by compliance rate
Measured: 2 years
Calculated dietary compliance
Analysed by comparing macronutrient content assessed via 3 day food diaries to advised macronutrient content.
Measured: 2 years
MCT compliance
Dose of MCT taken compared to dose advised.
Measured: 2 years
Ketosis levels
Self reported urinary ketone levels twice daily for first 6 weeks then once per week thereafter and blood ketone and glucose levels weekly.
Measured: 2 years
Dietetic time required for interventions
Dietetic time spent on clinical and non clinical activities relating to the trial.
Measured: 2 years
Protocol refinements required
Number of deviations from the protocol including reasons for deviations.
Measured: 2 years
Sample size estimates for future trials
Number of participants required for future phase III clinical trials
Measured: 2 years
Quality of life
Change in quality of life assessed through EORTC QLQ C30 and BN 20 questionnaires
Measured: 2 years
Food acceptability
Change in food acceptability assessed through food acceptability questionnaire
Measured: 2 years
Gastrointestinal side effects
Number of reported gastrointestinal side effects assessed through EORTC QLQ C30 questionnaire and Common Terminology Criteria for Adverse Events.
Measured: 2 years
Changes to biochemical markers
Changes to biochemical markers (renal, bone, LFT, lipid profiles) during the duration of the diet.
Measured: 2 years
Anthropometric changes
Changes to anthropometry (weight, body mass index, fat mass, muscle circumference, hand grip strength) during the duration of the diet.
Measured: 2 years
Completeness of data
Number of complete data sets for all trial outcomes
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2017
- Study start1 Apr 2017
- Primary completion5 Mar 2019
- Study completion5 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- MKD and MCT ketogenic diets
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- Walton Centre NHS Foundation Trust, Vitaflo International, Ltd
- Responsible party
- Principal investigator, Michael Jenkinson, University of Liverpool
- Investigators
- Michael D Jenkinson, PhD, FRCS, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03075514
- Sponsor's protocol ID
- UoL001277
- Acronym
- KEATING
- Status last verified
- Apr 2019
- First submitted
- 28 Feb 2017
- Last updated
- 4 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29209515
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketogenic Diets as an Adjuvant Therapy in Glioblastoma: A Randomised Pilot Trial
- ClinicalTrials.gov ID
- NCT03075514
- Acronym / sponsor ID
- KEATING / UoL001277
- Conditions
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma, Adult
- Keywords
- ketogenic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- Walton Centre NHS Foundation Trust, Vitaflo International, Ltd
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 5 Mar 2019 (actual)
- Study completion
- 5 Mar 2019 (actual)
- First posted
- 9 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- MKD and MCT ketogenic diets
| Arm | Type | Receives |
|---|---|---|
| Modified ketogenic diet (MKD) | Active comparator | Other: MKDMKD: 80% fat and 5% carbohydrate (% of total energy requirements per day). |
| Medium chain triglyceride (MCT) diet | Active comparator | Other: MCTMCT: 75% fat (30% of which is medium chain fatty acids taken as a supplement) and 5% carbohydrate (% of total energy requirements per day). |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- Having prior use of KD
- Kidney dysfunction
- Liver dysfunction
- Gall bladder dysfunction
- Metabolic disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MKDModified ketogenic diet | Other | Modified ketogenic diet (MKD) |
| MCTMedium chain triglyceride ketogenic diet | Other | Medium chain triglyceride (MCT) diet |
Primary outcome
To assess retention and drop out rates
Time frame: 12 weeks
Number of patients who start randomized treatment as a proportion of the number randomized ;
To assess retention and drop out rates
Time frame: 12 weeks
The number of patients who complete 12 weeks as a proportion of the number randomized
To assess retention and drop out rates
Time frame: 12 weeks
Description of barriers and facilitators to data collection and participant retention
To assess retention and drop out rates
Time frame: 12 weeks
The time to dietary discontinuation
19 secondary outcomes
Estimation of recruitment rates
Time frame: 12 months
Enrollment of patients
Time frame: 12 months
Enrollment of patients
Time frame: 12 months
Enrollment of patients
Time frame: 12 months
Long term retention
Time frame: 2 years
Dietary adjustments required to achieve ketosis
Time frame: 2 years
Self reported dietary compliance
Time frame: 2 years
Calculated dietary compliance
Time frame: 2 years
MCT compliance
Time frame: 2 years
Ketosis levels
Time frame: 2 years
Dietetic time required for interventions
Time frame: 2 years
Protocol refinements required
Time frame: 2 years
Sample size estimates for future trials
Time frame: 2 years
Quality of life
Time frame: 2 years
Food acceptability
Time frame: 2 years
Gastrointestinal side effects
Time frame: 2 years
Changes to biochemical markers
Time frame: 2 years
Anthropometric changes
Time frame: 2 years
Completeness of data
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2019.
- Derived from this study: PubMed 29209515Martin-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.
- Individual participant dataSharing planned: No
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael D Jenkinson, PhD, FRCS principal investigator
University of Liverpool
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MKD and MCT in people with Glioblastoma and Glioblastoma Multiforme, run by University of Liverpool at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess retention and drop out rates (time frame: 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03075514, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2019.