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Trial registered on ANZCTR


Trial ID
ACTRN12614001027606
Ethics application status
Approved
Date submitted
10/09/2014
Date registered
24/09/2014
Date last updated
24/09/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
The use of a low carbohydrate, high fat diet for the treatment of epilepsy in adults
Scientific title
The efficacy of the Modified Atkins Diet for seizure reduction in Australian adults with medically refractory epilepsy.
Secondary ID [1] 285314 0
Nil known
Universal Trial Number (UTN)
U1111-1161-5923
Trial acronym
The MADE Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medically refractory epilespy 293028 0
Condition category
Condition code
Neurological 293298 293298 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After a four week, prospective baseline screening period, participants will be randomised to immediate or delayed commencement of the modified atkins diet for epilepsy (MADE). The MADE is a low carbohydrate, high fat diet. Total carbohydrate intake is limited to 15-20g per day, added fats are encouraged and intake for carbohydrate-free food and fluids is allowed. Participants will be instructed by a dieititian on the dietary modifications and will be given an information booklet including carbohydrate counting, meal and recipe ideas and label reading. The participants will follow the diet a period of three months and record the number of seizures they have per month compared to the baseline period. Participants will then have the option to continue on the diet for up to twelve months with regular follow up. During the trial participants will be reviewed regularly through face-to-face 30-60 minute consultations by the dietitian and a Neurologist and monitored for adverse events. The visits will occur at baseline, at the commencement of the diet, two weeks after starting the diet and at one month and three months after commencing the diet. Participants choosing to remain on the diet for longer than three months, will be followed up everyone three months for one year. Monitoring will include blood tests, urine ketone testing and food and seizure diaries.
Intervention code [1] 290226 0
Lifestyle
Intervention code [2] 290297 0
Treatment: Other
Comparator / control treatment
Participants in the control group, following the baseline screening period, will continue on their normal/usual diet for 14 weeks. They will then start on the MADE as per the intervention group.
Control group
Active

Outcomes
Primary outcome [1] 293133 0
Frequency of seizures per 28 days as recorded in the seizure diary
Timepoint [1] 293133 0
After 3 months on the modified atkins diet
Secondary outcome [1] 310424 0
Compliance with the dietary restrictions. This will be assessed using patient reported food intake diaries kept for 4 days prior to each study visit. The participant will complete urine ketone testing at home, daily for the first two weeks after commencing on the diet and then twice weekly there after whist on the diet. The urine ketone diaries will be reviewed at each study visit.
Timepoint [1] 310424 0
At 1 month, 3 months and if participants continue on the diet at 6, 9 and 12 month
Secondary outcome [2] 310499 0
Frequency of secondarily generalised tonic clonic seizures in patients with focal epilepsy as recorded in the seizure diary
Timepoint [2] 310499 0
At 1 month, 3months and if participants continue on the diet at 6, 9 and 12 months
Secondary outcome [3] 310500 0
Safety of the diet by monitoring serum fasting cholesterol, triglycerides and glucose. Renal function will be monitored by serum urea and creatinine levels and hepatic function by serum liver function tests.
Timepoint [3] 310500 0
At 1 month, 3 months and if participants continue on the diet at 6, 9 and 12 months
Secondary outcome [4] 310501 0
Quality of life score using the QOLIE-89
Timepoint [4] 310501 0
At baseline and 3 months and if participants continue of the diet at 12 months
Secondary outcome [5] 310502 0
Changes in body composition using weight and bioelectrical impedance spectroscopy to assess changes in fat and fat free mass
Timepoint [5] 310502 0
At baseline, 3 months and participants who continue on the diet at 6, 9 and 12 months

Eligibility
Key inclusion criteria
Aged 18-75 years
Diagnosed epilepsy, whether taking AEDs or not, experiencing two or more seizures in four weeks of one or more of the following types of seizures:
complex partial seizures (focal dyscognitive seizures)
secondary generalised tonic clonic seizures
simple partial seizures with motor features
primary generalised tonic clonic seizures
tonic seizures
atonic seizures
No changes in AEDs or vagus nerve stimulation (VNS) settings for one month prior to enrolment
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Under 18 years of age
Body mass index < 18.5kg/m2
Patients with cluster seizures or who are unable to count or describe their seizures
Patients experiencing myoclonic or absence seizures only
Patients experiencing non-epileptic seizures
Diabetes Mellitus
Fatty acid or amino acid oxidation disorders
Pre-existing renal and/or liver failure
Currently on the ketogenic diet
Prior history of eating disorders
Females who are pregnant or breastfeeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified randomisation for participants on anti-epileptic drugs and participants not on anti-epileptic drugs using randomisation software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Primary outcomes in the 2 groups during the treatment phase will be compared. A sample size of 58 is required (29 participants in each group), to achieve a confidence interval of 0.8 with alpha=0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 2972 0
Royal Melbourne Hospital - City campus - Parkville

Funding & Sponsors
Funding source category [1] 289933 0
Hospital
Name [1] 289933 0
Royal Melbourne Hospital
Address [1] 289933 0
Grattan Street
Parkville VIC 3050
Country [1] 289933 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
Grattan Street
Parkville VIC 3050
Country
Australia
Secondary sponsor category [1] 288624 0
None
Name [1] 288624 0
Address [1] 288624 0
Country [1] 288624 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291649 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 291649 0
Royal Melbourne Hospital
Grattan Street
Parkville VIC 3050
Ethics committee country [1] 291649 0
Australia
Date submitted for ethics approval [1] 291649 0
Approval date [1] 291649 0
15/07/2014
Ethics approval number [1] 291649 0
2014.004

Summary
Brief summary
Epilepsy affects an estimated 225,000 Australians. Approximately one-third of people with epilepsy still experience seizures whilst on medications. They may be on maximum therapy or are unable to tolerate the side-effects of anti-seizure medications. There is emerging evidence to show a very low carbohydrate diet, known as the Modified Atkins Diet for Epilepsy (MADE), may improve seizure control, with relatively low side-effects. The use of this dietary therapy has not previously been studied in Australian adults.
This research aims to investigate if Australian adults with epilepsy are able to comply with the dietary modifications of the MADE and to assess if participants experience a reduction in the number of seizures whilst on the diet.
Participants will be seen regularly during the study by a Neurologist to monitor for any side-effects of the diet. A Dietitian will provide education, support and resources for those participating in the study on a regular basis.
We anticipate most participants will be able to implement the dietary modification of the MADE. It is expected participants will experience up to half the number of seizures than normal whilst on the diet with minimal side-effects. A reduction in seizures can significantly improve the quality of life and overall health status of people with epilepsy who do not respond to medication management.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51346 0
Ms Neha Kaul
Address 51346 0
Dept of Clinical Nutrition
Level 4 North Allied Health
Royal Melbourne Hospital
Grattan Street
Parkville
VIC 3050
Country 51346 0
Australia
Phone 51346 0
+61 3 9342 4658
Fax 51346 0
Email 51346 0
neha.kaul@mh.org.au
Contact person for public queries
Name 51347 0
Ms Neha Kaul
Address 51347 0
Dept of Clinical Nutrition
Level 4 North Allied Health
Royal Melbourne Hospital
Grattan Street
Parkville
VIC 3050
Country 51347 0
Australia
Phone 51347 0
+61 3 9342 4658
Fax 51347 0
Email 51347 0
neha.kaul@mh.org.au
Contact person for scientific queries
Name 51348 0
Ms Neha Kaul
Address 51348 0
Dept of Clinical Nutrition
Level 4 North Allied Health
Royal Melbourne Hospital
Grattan Street
Parkville
VIC 3050
Country 51348 0
Australia
Phone 51348 0
+61 3 9342 4658
Fax 51348 0
Email 51348 0
neha.kaul@mh.org.au