ANZCTR - Registration

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

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]

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

Condition category

Condition code

Neurological

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

1.Retention, measured as the number and proportion taking treatment over the 48 week treatment period.

Timepoint [1]

48 weeks

Primary outcome [2]

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]

weeks 1, 2, 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 55, 57

Secondary outcome [1]

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]

weeks 1, 2, 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 55, 57

Secondary outcome [2]

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]

weeks 1, 2, 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 55, 57

Secondary outcome [3]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

17/02/2015

Actual

17/02/2015

Date of last participant enrolment

Anticipated

31/12/2015

Actual

1/11/2015

Date of last data collection

Anticipated

Actual

9/08/2017

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Royal Melbourne Hospital - City campus - Parkville

Recruitment postcode(s) [1]

3050 - Royal Melbourne Hospital

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Queensland

Address [1]

School of Biomedical Sciences
Department of Pharmacology
Brisbane QLD 4072

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health

Ethics committee address [1]

PO Royal Melbourne Hospital
Parkville VIC 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

20/10/2014

Ethics approval number [1]

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

Prof Terence O'Brien

Address

Department of Medicine
The University of Melbourne
The Royal Melbourne Hospital
4th Floor Clinical Sciences Building
Royal Parade, Parkville VIC 3050

Country

Australia

Phone

+ 61 3 8344 5490

Fax

N/A

[email protected]

Contact person for public queries

Name

Jack Germaine

Address

The Royal Melbourne Hospital
4th Floor Clinical Sciences Building
Royal Parade, Parkville VIC 3050

Country

Australia

Phone

+61 3 9342 4658

Fax

N/A

[email protected]

Contact person for scientific queries

Name

Karin Borges

Address

University of Queensland
School of Biomedical Sciences
Department of Pharmacology
Brisbane QLD 4072

Country

Australia

Phone

+61 7 3365 3113

Fax

N/A

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Open-label long-term treatment of add-on triheptanoin in adults with drug-resistant epilepsy.	2020	https://dx.doi.org/10.1002/epi4.12391

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically