Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000784516p
Ethics application status
Submitted, not yet approved
Date submitted
20/05/2024
Date registered
26/06/2024
Date last updated
26/06/2024
Date data sharing statement initially provided
26/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Ketogenic diet therapy for chronic migraines
Scientific title
Evaluating the safety, tolerability and efficacy of the ketogenic diet therapy in adults with chronic migraines
Secondary ID [1] 312025 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 333631 0
Condition category
Condition code
Neurological 330318 330318 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study participants will undergo a 12-week trial of a modified ketogenic diet (MKD) for the prevention of chronic migraine.

Participants will undergo a 5-week baseline/screening period, and then under the supervision of an expert dietitian, transition to a MKD for 12 weeks. The diet will contain a ratio of 75% fat, 20% protein and 5% carbohydrates, however calorie quantities will be tailored to each participant. Participants will receive initial counselling and resources (roughly 1 hour duration for initial consultation), and regular review with the study dietitian (roughly 30 minute duration for subsequent visits on monthly basis). Initial consultation will be face-to-face to ensure anthropometrics and baseline blood tests can be collected. Subsequent visits can be face-to-face, telehealth or telephone reviews based on patient preference.

Study activities will include daily urinary ketone monitoring, and two-weeks of continuous glucose monitoring (CGM) while on therapy, in addition to standard of care blood safety monitoring. Adherence will be monitored with a food diary and urinary ketones. The continuous glucose monitoring will occur during weeks 1-2 of the study (prior to starting ketogenic diet) and also weeks 17-18 of the study (weeks 11 and 12 of the diet).

The study resources provided are used in clinical practice and clinical trials involving the ketogenic diet at our centre. They have been designed by Dr Neha Kaul, Senior Dietitian. The materials have been reviewed and approved by consumers and by the institution’s human research ethics committee.
Intervention code [1] 328473 0
Treatment: Other
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338073 0
1. Proportion of participants remaining on modified ketogenic diet (MKD) after 12 weeks
Timepoint [1] 338073 0
12 weeks, or at conclusion of the study
Primary outcome [2] 338438 0
2. Rate of discontinuation due to an adverse event
Timepoint [2] 338438 0
12 weeks, or at the conclusion of the study
Secondary outcome [1] 434378 0
Rate of adverse events such as unintentional weight change, nausea, vomiting, constipation, diarrhoea, abnormal blood lipid profile or vitamin and/or mineral deficiencies
Timepoint [1] 434378 0
Adverse events will be assessed weekly throughout the 12-week intervention period
Secondary outcome [2] 434393 0
Assess the efficacy of MKD as a preventative therapy in chronic migraine
Timepoint [2] 434393 0
Headache frequency will be assessed after 12 weeks of therapy, or at study conclusion.
Secondary outcome [3] 434394 0
Assess the efficacy of MKD as a preventative therapy in chronic migraine
Timepoint [3] 434394 0
Healthcare utilisation and acute medication use will be assessed during week 9-12 of the study, in comparison for the 4 week baseline period
Secondary outcome [4] 436730 0
Migraine-specific quality of life
Timepoint [4] 436730 0
Baseline, monthly whilst on the diet therapy and at conclusion of the study
Secondary outcome [5] 436731 0
Mood
Timepoint [5] 436731 0
Baseline, monthly whilst on the diet therapy and at conclusion of the study
Secondary outcome [6] 436732 0
Productivity
Timepoint [6] 436732 0
Baseline, monthly whilst on diet therapy and at conclusion of the study
Secondary outcome [7] 436733 0
Sleep
Timepoint [7] 436733 0
Baseline, monthly whilst on diet therapy and at conclusion of the study
Secondary outcome [8] 436734 0
Quality of life
Timepoint [8] 436734 0
Baseline, monthly whilst on diet therapy and at conclusion of study
Secondary outcome [9] 436739 0
Rating of change
Timepoint [9] 436739 0
Baseline, monthly whilst on diet therapy and at conclusion of study
Secondary outcome [10] 436741 0
Anxiety
Timepoint [10] 436741 0
Baseline, monthly whilst on diet therapy and at the conclusion of study

Eligibility
Key inclusion criteria
- Aged 18-60 at time of enrolment
- At least a 1-year history of migraine, and current diagnosis of chronic migraine for three months (The International Classification of Headache Disorders 3 (ICHD-3 criteria)
- No change in migraine treatment in the preceding three months prior to enrolment
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Body mass index less then 18.5kg/m2
- Fatty acid or amino acid oxidation disorder
- Pre-existing renal and/or liver failure
- Known diagnosis of diabetes mellitus
- History of pancreatitis
- HbA1c greater then or equal to 6%
- Prior history of eating disorder that the treating clinician or dietitian reasonably considers may be exacerbated by dietary therapy
- Women who are pregnant, breastfeeding or planning to become pregnant during the study
- Allergy to medical adhesives
- Unable to participate in study visits.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The efficacy analyses will be based on an intention to treat analysis. The primary outcome, retention of patients, will be assessed with a pre-determined outcome of 75% of patients remaining on therapy. The primary efficacy outcome, greater then or equal to 50% reduction in MHD, will be summarised using median and inter-quartile ranges as it is anticipated to be non-normally distributed. For secondary efficacy and follow-up outcomes, continuous variables will be summarised using means and standard deviations or medians and inter-quartile ranges depending on the underlying data distribution. Categorical variables will be expressed as counts and proportions. Exploratory univariable analysis will be conducted using Student’s t-test, Mann-Whitney U test, Chi-squared or Fisher’s exact tests where appropriate. Safety and tolerability outcomes, such as adverse events, will be descriptively summarized.
All statistical tests will be performed by using statistical software packages R (R Core Team), Stata (StataCorp) or SPSS (IBM Corp).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
1/08/2025
Actual
Date of last data collection
Anticipated
12/12/2025
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26474 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 42452 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 316376 0
Charities/Societies/Foundations
Name [1] 316376 0
International Headache Society
Country [1] 316376 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
Country
Australia
Secondary sponsor category [1] 318562 0
University
Name [1] 318562 0
Monash University
Address [1] 318562 0
Country [1] 318562 0
Australia
Other collaborator category [1] 283014 0
University
Name [1] 283014 0
Monash University
Address [1] 283014 0
Country [1] 283014 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 315184 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315184 0
https://www.alfredhealth.org.au/research/ethics-research-governance
Ethics committee country [1] 315184 0
Australia
Date submitted for ethics approval [1] 315184 0
10/04/2024
Approval date [1] 315184 0
Ethics approval number [1] 315184 0

Summary
Brief summary
This study is a prospective single-group cohort study to evaluate the safety and tolerability of a modified ketogenic diet as an adjunct preventative treatment in adults with chronic migraine.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133918 0
Dr Jason Ray
Address 133918 0
Alfred Health, 55 Commercial Rd, Melbourne, VIC 3004
Country 133918 0
Australia
Phone 133918 0
+61 390762470
Fax 133918 0
Email 133918 0
j.ray@alfred.org.au
Contact person for public queries
Name 133919 0
Jason Ray
Address 133919 0
Alfred Health, 55 Commercial Rd, Melbourne, VIC 3004
Country 133919 0
Australia
Phone 133919 0
+61 390762470
Fax 133919 0
Email 133919 0
j.ray@alfred.org.au
Contact person for scientific queries
Name 133920 0
Jason Ray
Address 133920 0
Alfred Health, 55 Commercial Rd, Melbourne, VIC 3004
Country 133920 0
Australia
Phone 133920 0
+61 390762470
Fax 133920 0
Email 133920 0
j.ray@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.