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Trial registered on ANZCTR


Registration number
ACTRN12615000406505
Ethics application status
Approved
Date submitted
19/02/2015
Date registered
30/04/2015
Date last updated
17/01/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to assess the long term retention on treatment and long-term safety and tolerability of Triheptanoin in male and female participants with drug-resistant epilepsy
Scientific title
An open-label extension study of oral Triheptanoin as an add-on treatment to adolescent and adult participants with medically refractory epilepsy
Secondary ID [1] 286217 0
Nil
Universal Trial Number (UTN)
N/A
Trial acronym
TRIP-Ex
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medically refractory epilepsy 294265 0
Condition category
Condition code
Neurological 294581 294581 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: Triheptanoin (triglyceride of heptanoate), a stable, edible tasteless oil that has been used in patients with metabolic disorders.
Dose:initial dose (e.g. 15ml oil/day)the dose is escalated every week.
Treated with up to 35% of caloric input triheptanoin (max 100 ml oil/day). The oil will be added to a normal diet, titrated up over 3 weeks and full dose given for a period of 48 weeks.
Route: Orally three times daily (with meals) for 48 weeks
During the full time of the study seizures, adverse events,
side effects, weight and quality of life will be recorded. To improve adherence the participants will have regular contact with a dietitian face to face and via phone. Participants/carers will fill in a food diary and treatment diary to monitor compliance and return the used and unused bottles of oil.
Intervention code [1] 291235 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294350 0
1.Retention, measured as the number and proportion taking treatment over the 48 week treatment period.
Timepoint [1] 294350 0
48 weeks
Primary outcome [2] 294806 0
2.Safety, measured as the number of adverse events that are causally (defined as probably and definitely) related to study intervention over the 48 week treatment period.
The major side effect is a change in bowel habits (constipation or diarrhoea).
Timepoint [2] 294806 0
weeks 1, 2, 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 55, 57
Secondary outcome [1] 313084 0
1.Tolerated dose per day, as measured as the average treatment dose actually taken over the full 48 week full dose treatment period.
Assessed by dose review at each visit
Timepoint [1] 313084 0
weeks 1, 2, 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 55, 57
Secondary outcome [2] 314093 0
2. Seizure frequency over the 48 week full dose treatment period as compared to the 8 week baseline period from the TRIP-E study.
Assessed by seizure diary
Timepoint [2] 314093 0
weeks 1, 2, 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 55, 57
Secondary outcome [3] 314094 0
3. Responder rate: the proportion of participants who show equal to 50% improvement in seizure frequency over the 48 week full dose treatment period as compared to the baseline period from the TRIP-E study.
Assessed by seizure diary
Timepoint [3] 314094 0
weeks 1, 2, 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 55, 57

Eligibility
Key inclusion criteria
TRIP-E study (ACTRN12612000226808) for cross referencing purposes

1. Participants randomised in the TRIP-E study and who finished the treatment period with appropriate compliance with diet and study procedures.
2. Ability to give informed consent (Participant, parent or person responsible)
3. Females of childbearing potential must have a negative serum betahCG at Visit 1 and either abstain or use acceptable contraception for the duration of the trial.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants with a severe intellectual handicap
2. History of major psychiatric morbidity (such as psychiatric illness requiring hospitalisation or history of psychosis or major depression)
3. Participants with history of substance abuse, eating disorders or irritable bowel syndrome
4. Females who are pregnant or breast feeding
5. Participants with disorders affecting medium and short chain fatty acid oxidation.

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)
Up to 60 male and female participants (equal to or greater than 16 years old) with drug-resistant epilepsy will be invited to participate in the TRIP-Ex study upon completion of the TRIP-E study. Enrolment into the TRIP-Ex study (Visit 1) may coincide with Visit 7 of the TRIP-E study. Participants need not repeat the screening assessments that are conducted during TRIP-E Visit 7 at Visit 1 of this study (TRIP Ex). A calculated dose of treatment will be dispensed to the participant. There is an uptitration and downtitration period.
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
Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis
Statistical analysis will be largely descriptive in endpoints noted above for the co-primary endpoints retention and safety, as well as the secondary endpoint responder rate and dietary changes. Averages and 95% confidence intervals will be calculated for the secondary endpoints; and median and ranges of scores will be reported for the questionnaires for the different visits. Scores will be compared in individual participants over time. The number and percentage of participants showing improvements in scores will be reported.

Recruitment
Recruitment status
Completed
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] 3480 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 9248 0
3050 - Royal Melbourne Hospital

Funding & Sponsors
Funding source category [1] 290783 0
University
Name [1] 290783 0
University of Queensland
Address [1] 290783 0
School of Biomedical Sciences
Department of Pharmacology
Brisbane QLD 4072
Country [1] 290783 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
School of Biomedical Sciences
Department of Pharmacology
Brisbane QLD 4072
Country
Australia
Secondary sponsor category [1] 289467 0
None
Name [1] 289467 0
Address [1] 289467 0
Country [1] 289467 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292414 0
Melbourne Health
Ethics committee address [1] 292414 0
PO Royal Melbourne Hospital
Parkville VIC 3050
Ethics committee country [1] 292414 0
Australia
Date submitted for ethics approval [1] 292414 0
Approval date [1] 292414 0
20/10/2014
Ethics approval number [1] 292414 0
2014.161

Summary
Brief summary
This is an open label study designed to assess the long term retention on treatment and long-term safety and tolerability of Triheptanoin in participants with drug-resistant epilepsy.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 55130 0
Prof Terence O'Brien
Address 55130 0
Department of Medicine
The University of Melbourne
The Royal Melbourne Hospital
4th Floor Clinical Sciences Building
Royal Parade, Parkville VIC 3050
Country 55130 0
Australia
Phone 55130 0
+ 61 3 8344 5490
Fax 55130 0
N/A
Email 55130 0
obrientj@unimelb.edu.au
Contact person for public queries
Name 55131 0
Mr Jack Germaine
Address 55131 0
The Royal Melbourne Hospital
4th Floor Clinical Sciences Building
Royal Parade, Parkville VIC 3050
Country 55131 0
Australia
Phone 55131 0
+61 3 9342 4658
Fax 55131 0
N/A
Email 55131 0
Jack.Germaine@mh.org.au
Contact person for scientific queries
Name 55132 0
Dr Karin Borges
Address 55132 0
University of Queensland
School of Biomedical Sciences
Department of Pharmacology
Brisbane QLD 4072
Country 55132 0
Australia
Phone 55132 0
+61 7 3365 3113
Fax 55132 0
N/A
Email 55132 0
k.borges@uq.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary