Trial registered on ANZCTR


Trial ID
ACTRN12612000226808
Ethics application status
Approved
Date submitted
15/02/2012
Date registered
22/02/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A safety and feasibility study of oral Triheptanoin as an add on treatment for patients (12 years or older) with medical refractory epilepsy.
Scientific title
A Phase IIa randomized double-blind placebo controlled study to evaluate the safety and feasibility of oral triheptanoin as an add-on treatment to adolescent and adult patients with medically refractory epilepsy
Secondary ID [1] 279945 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
TRIP - E

Health condition
Health condition(s) or problem(s) studied:
Medical refractory epilepsy 285862 0
Condition category
Condition code
Neurological 286045 286045 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The patient will be up titrated to a maximum tolerated dose of Triheptanoin during a three week titration period. (Start dose 15 ml) The total daily dose will be between 15 and 100ml daily depending on the patients tolerability (Up to 35% of caloric input per day). Patients will be take the maximum tolerated dose over a period of 16 weeks and assessed during this time. Patients will take Triheptanoin orally three to four times per day with meals. They will be asked to complete a food and seizure diary
Intervention code [1] 284275 0
Treatment: drugs
Comparator / control treatment
The patient will be up titrated to a maximum tolerated dose of C8/C10 (Comparator) during a three week titration period. (Start dose 15 ml) The total daily dose will be between 15 and 100ml daily depending on the patients tolerability (Up to 35% of caloric input per day). Patients will be take the maximum tolerated dose over a period of 16 weeks and assessed during this time. Patients will take C8/C10 (Comparator)orally three to four times per day with meals. They will be asked to complete a food and seizure diary
Control group
Placebo

Outcomes
Primary outcome [1] 286528 0
Safety. Possible adverse events include gastrointestinal upset and diarrhoea.
Timepoint [1] 286528 0
Monitored weekly during 3 week titration period and then four weekly over the 16 week treatment period. Safety will be assessed based on reported adverse events.
Secondary outcome [1] 296088 0
Complience with treatment
Timepoint [1] 296088 0
Will be monitored weekly during the titration period and then 4 weekly during the 16 week treatment period. Complience will be assessed by amount of oil returned at each study visit.
Secondary outcome [2] 296151 0
Tolerability of treatment
Timepoint [2] 296151 0
Will be monitored weekly during the titration period and then 4 weekly during the 16 wekk treatment period. Tolerability will be assessed based on discussions with the patient, assessment of the food diary and assessment of adverse events.

Eligibility
Key inclusion criteria
Male or female patients (12 years or older) with epilepsy who have experienced at least 4 seizures of an eligible type per month over two months prior to enrolment despite treatment with at least one anti-epileptic drug at clinically appropriate doses. (Eligible seizure types are: complex partial seizures (focal dyscognitive seizures), secondary generalised seizures, simple partial seizures with motor features, primary generalised seizures, tonic seizures, atonic seizures) Patients anti-epileptic drugs over the four weeks prior to enrolment must remain stable with no change.
Patients must be able to provide informed consent.
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with a severe intellectual handicap

Patients with a history of major psychiatric morbidity (such as psychiatric illness requiring hospitalisation or history of psychosis or major depression)

Patients with history of substance abuse

Patients with a history of having had psychogenic non-epileptic seizures

Patients who have seizure clusters or other reasons that make counting of numbers of seizures inaccurate

Females who are pregnant or breast feeding

Patients with disorders affecting medium and short chain fatty acid oxidation. This includes medium-chain acyl-CoA dehydrogenase deficiency - MCAD, short-chain acyl-CoA dehydrogenase deficiency - SCAD, short-chain-3 hydroxyacyl-CoA dehydrogenase deficiency –SCHAD and HMG CoA (3-hydroxy-3-methyl-glutaryl-CoA) synthase deficiency.

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)
Subjects will be randomised to recieve either Triheptanoin or Placebo at Week 8 (Visit 2). Patients will be assigned a unique Identification Number, which will be allocated in ascending order of random numbers based on the predetermined randomisation schedule, and according to their chronological order of inclusion in the study. Subjects will then be allocated corresponding treatment, labelled with the same number. Confirmation of the treatment number allocated will be documented in the drug accountability records and recorded in the CRF. Triheptanoin oil and placebo oil will be identical in appearance. The nature of treatment each subject will receive will not be disclosed to the investigator, study site personnel or subjects.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation schedule (1:1 ratio triheptanoin to placebo oil treatments) will be prepared by a statistician prior to the start of the study and stratified by each study centre. This schedule will be administered by the CRO, NTA.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 2
Type of endpoint(s)
Safety

Recruitment
Anticipated date of first participant enrolment
1/04/2012
Actual date of first participant enrolment
30/07/2012
Anticipated date last participant enrolled
Actual date last participant enrolled
6/03/2015
Target sample size
60
Actual sample size
58
Recruitment status
Closed: follow-up complete
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 284714 0
University
Name [1] 284714 0
University of Queensland
Address [1] 284714 0
St Lucia, Brisbane QLD 4072
Country [1] 284714 0
Australia
Funding source category [2] 284715 0
Charities/Societies/Foundations
Name [2] 284715 0
Epilepsy Therapy Project
Address [2] 284715 0
PO Box 742
10N Pendleton St
Middleburg VA 20118
Country [2] 284715 0
United States of America
Primary sponsor type
University
Name
University of Queensland
Address
St Lucia, Brisbane, QLD 4072
Country
Australia
Secondary sponsor category [1] 283615 0
None
Name [1] 283615 0
Address [1] 283615 0
Country [1] 283615 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286720 0
Royal Melbourne Hospital
Ethics committee address [1] 286720 0
Grattan Street Parkville 3050
Ethics committee country [1] 286720 0
Australia
Date submitted for ethics approval [1] 286720 0
22/02/2012
Approval date [1] 286720 0
30/03/2012
Ethics approval number [1] 286720 0
HREC 2012.059

Summary
Brief summary
A study to determine the safety, tolerability and complience tripheptanoin oil, taken as an oral supplement by patients 12 years and older, who have medical refractory epilepsy.
Trial website
nil
Trial related presentations / publications
nil
Public notes

Contacts
Principal investigator
Name 33779 0
Prof Terence O'Brien
Address 33779 0
Royal Melbourne Hospital
4th Floor Clinical Sciences Building
Royal Parade, Parkville VIC 3050
Country 33779 0
Australia
Phone 33779 0
+61 3 9 342 4658
Fax 33779 0
Email 33779 0
obrientj@unimelb.edu.au
Contact person for public queries
Name 17026 0
Dr Dr Karin Borges
Address 17026 0
Department of Pharmacology
School of Biomedical Sciences
University of Queensland
Brisbane, QLD 4072
Australia
Country 17026 0
Australia
Phone 17026 0
+61 7 3365 3113
Fax 17026 0
Email 17026 0
k.borges@uq.edu.au
Contact person for scientific queries
Name 7954 0
Dr Dr Karin Borges
Address 7954 0
Department of Pharmacology
School of Biomedical Sciences
University of Queensland
Brisbane, QLD 4072
Australia
Country 7954 0
Australia
Phone 7954 0
+61 7 3365 3113
Fax 7954 0
Email 7954 0
k.borges@uq.edu.au