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Trial registered on ANZCTR


Registration number
ACTRN12625000095460p
Ethics application status
Submitted, not yet approved
Date submitted
8/12/2023
Date registered
29/01/2025
Date last updated
29/01/2025
Date data sharing statement initially provided
29/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
TRI-ME: Trimetazidine to treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A double-blind, randomised, placebo-controlled efficacy trial
Scientific title
TRI-ME: Trimetazidine to treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A double-blind, randomised, placebo-controlled efficacy trial
Secondary ID [1] 311139 0
Nil known
Universal Trial Number (UTN)
Trial acronym
TRI-ME
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 332297 0
Condition category
Condition code
Other 329012 329012 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1) Intervention: Trimetazidine
2) Dose: a single 35mg tablet per dose, twice daily.
3) Duration: 8 weeks.
4) Mode of Administration: Oral tablet.
5) Adherence monitoring: Participants are required to return all medication bottles for double tablet count by the trial pharmacist and trial coordinator.
Intervention code [1] 327581 0
Treatment: Drugs
Comparator / control treatment
Control treatment: Matched placebo tablets (pink round film-coated tablets consisting of microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate and sodium stearyl fumarate), A single 35mg tablet per dose, twice daily, for 8 weeks.

To monitor treatment adherence, participants will be instructed to return all containers to allow tablet counts by the trial pharmacist. The tablets may be double-counted by the trial coordinator prior to destruction.
Control group
Placebo

Outcomes
Primary outcome [1] 336807 0
The primary outcome is the between-group differential change for ME/CFS symptoms from baseline to endpoint on the Chalder Fatigue Scale (CFQ),
Timepoint [1] 336807 0
Conducted at all visits - Baseline (intervention commencement) and at weeks 2, 4 and 8 (primary endpoint).
Secondary outcome [1] 429722 0
Change in other symptomatic measures of ME/CFS symptomology including post-exertional malaise, fatigue, sleep, pain, cognitive impairment and autonomic, neuroendocrine and immune disturbance assessed as a composite outcome.
Timepoint [1] 429722 0
Conducted at Baseline and at Week 8 (secondary endpoint)
Secondary outcome [2] 430162 0
Change in severity of depressive symptoms (i.e. reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic and suicidal thoughts) assessed as a composite outcome.
Timepoint [2] 430162 0
Conducted at Baseline and at Week 8
Secondary outcome [3] 430163 0
Change in physical fatigue
Timepoint [3] 430163 0
Conducted at Baseline and at Week 8
Secondary outcome [4] 430164 0
Change in severity of sleeping problems
Timepoint [4] 430164 0
Conducted at Baseline and at Week 8
Secondary outcome [5] 430165 0
Change in day to day physical activities
Timepoint [5] 430165 0
Conducted at Baseline and at Week 8
Secondary outcome [6] 430166 0
Change in fatigue that impacts on physical, cognitive and psychosocial function assessed as a composite outcome.
Timepoint [6] 430166 0
Conducted at Baseline and at Week 8
Secondary outcome [7] 430168 0
Change in grip strength
Timepoint [7] 430168 0
Conducted at Baseline and at Week 8
Secondary outcome [8] 430169 0
Treatment and additional costs related to healthcare use
Timepoint [8] 430169 0
Conducted at Baseline and at Week 8
Secondary outcome [9] 434659 0
Change in self-reported measure of productivity
Timepoint [9] 434659 0
Conducted at Baseline and at Week 8
Secondary outcome [10] 434660 0
Change in impact of health on quality of life
Timepoint [10] 434660 0
Conducted at Baseline and at Week 8
Secondary outcome [11] 442863 0
Change in post exertional malaise
Timepoint [11] 442863 0
Conducted at Baseline and at Week 8

Eligibility
Key inclusion criteria
1) Aged 18 years or above;
2) Fulfil the criteria Canadian Consensus Criteria44 for ME/CFS diagnosis;
3) Willing and able to give informed consent prior to study enrolment and to comply with study procedures;
4) Ongoing use of contraception (if sexually active and of childbearing potential age);
5) Nominate a current treating physician.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) A known or suspected active and unstable systemic medical disorder that is deemed to affect the participant safety to enrol, determined by the PI or their delegate;
2) Any history of severe renal disease (e.g. eGFR < 30, renal failure), Parkinson’s disease, restless legs syndrome or other movement disorders;
3) A DSM-5 diagnosis of a current major psychiatric disorder (e.g., any of psychotic, bipolar, substance dependence, eating, or significant personality disorders);
4) Be currently pregnant or breastfeeding;
5) Have contraindications or intolerance or allergy to trimetazidine;
6) Initiate cognitive behavioural therapy and/or graded exercise, or other evidence-based treatments that may affect ME/CFS symptoms within 4 weeks before study entry;
7) Concurrently enrolled in another clinical trial;
8) Inability to comply with either the requirements of informed consent or the treatment protocol;
9) Current concomitant use of Monoamine oxidase inhibitors.
10) A clinically significant reading from safety blood tests that deem the participant ineligible, at a medically qualified site principal investigator’s discretion.

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)
The trial biostatistician and clinicians, and participants and their carers and physicians, will be blinded to group allocations. Allocation to treatment arms will occur in a 1:1 ratio using permutated block randomisation. An independent statistician will develop the permuted block randomisation with varying block sizes using a computer-generated randomisation plan and generate/retain the allocation list, which the site pharmacist or the pharmaceutical supplier will use to prepare medication bottles and kits. Bottles and study medication tablets of the active and placebo will look identical to conceal treatment allocation. Trial clinicians and/or researchers will allocate packs to participants sequentially.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation with varying block sizes created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/02/2025
Actual
Date of last participant enrolment
Anticipated
4/08/2028
Actual
Date of last data collection
Anticipated
29/09/2028
Actual
Sample size
Target
126
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 315394 0
Government body
Name [1] 315394 0
The National Health and Medical Research Council (NHMRC), Leadership 3 Investigator grant (GNT 2017131)
Country [1] 315394 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
75 Pigdons Rd, Waurn Ponds VIC 3216
Country
Australia
Secondary sponsor category [1] 320585 0
None
Name [1] 320585 0
Address [1] 320585 0
Country [1] 320585 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314312 0
Barwon Health HREC
Ethics committee address [1] 314312 0
Ethics committee country [1] 314312 0
Australia
Date submitted for ethics approval [1] 314312 0
26/06/2024
Approval date [1] 314312 0
Ethics approval number [1] 314312 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131146 0
Prof Michael Berk
Address 131146 0
IMPACT, Deakin University, HERB-B P.O. Box 281 Geelong, Victoria 3220
Country 131146 0
Australia
Phone 131146 0
+61 3 4215 3330
Fax 131146 0
Email 131146 0
michael.berk@deakin.edu.au
Contact person for public queries
Name 131147 0
Johnny Park
Address 131147 0
IMPACT, Deakin University, HERB-B P.O. Box 281 Geelong, Victoria 3220
Country 131147 0
Australia
Phone 131147 0
+61 3 5227 8077
Fax 131147 0
Email 131147 0
TRI-ME@deakin.edu.au
Contact person for scientific queries
Name 131148 0
Michael Berk
Address 131148 0
IMPACT, Deakin University, HERB-B P.O. Box 281 Geelong, Victoria 3220
Country 131148 0
Australia
Phone 131148 0
+61 3 4215 3330
Fax 131148 0
Email 131148 0
michael.berk@deakin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified clinical trial data will be available following publication of the primary data and a-priori secondary data.
When will data be available (start and end dates)?
Data will be available following publication of primary and a-priori secondary outcomes. No end date.
Available to whom?
Available to research staff with appropriate Human Research and Ethics Approval.
Available for what types of analyses?
All types, both individual-level analyses as well as meta-analyses.
How or where can data be obtained?
Data can be directly requested (via email: impact@deakin.edu.au) from the investigators and will be approved on a case-by-case arrangement.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
22354Study protocol    Intention to publish the study protocol


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.