Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000172606p
Ethics application status
Submitted, not yet approved
Date submitted
7/12/2022
Date registered
20/02/2023
Date last updated
20/02/2023
Date data sharing statement initially provided
20/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Low Dose Naltrexone in Fibromyalgia - A randomised controlled cross-over trial
Scientific title
The efficacy of Low Dose Naltrexone in Fibromyalgia - A randomised controlled cross-over trial
Secondary ID [1] 308528 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
fibromyalgia 328357 0
Condition category
Condition code
Other 325398 325398 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
Capsule for oral intake, containing active ingredient (naltrexone) 1.5mg daily for one week, 3mg daily next week, 4.5mg daily for subsequent 6 weeks (8 weeks total). May be taken at any regular time during the day. There is an additional control period (creating a crossover design) of four weeks of placebo once daily, which is randomised to the beginning or end of the treatment period, resulting in 12 weeks of capsule taking for the participants. There is no wash-out period between active and placebo capsules.
Study participants will be asked to return unused medicine at the end of the trial, and research team will have regular phone check-in (4-weekly) with them about their pain, during which investigators will verbally check on their compliance and unwanted effects.
Intervention code [1] 324970 0
Treatment: Drugs
Comparator / control treatment
Capsule for oral intake, containing excipient microcellulose 1.5mg daily for one week, 3mg daily next week, 4.5mg daily for subsequent 6 weeks (8 weeks total). May be taken at any regular time during the day.
Control group
Placebo

Outcomes
Primary outcome [1] 333250 0
Level of pain severity as measured by Fibromyalgia Impact Questionnaire, Revised (FIQR) (Symptoms Domain, Question 1): average pain intensity during the last 7 days on an 11- point rating scale (ranging from 0 = “no pain” to 10 = “unbearable pain”).
Timepoint [1] 333250 0
Outcomes will be measured at Visit 1 Commencement, Visit 2 (halfway: 6 weeks after commencement) and Visit 3 (Primary timepoints: 12 weeks after commencement) .
Secondary outcome [1] 416337 0
1. Impact of fibromyalgia: assessed by the FIQR total score
Timepoint [1] 416337 0
Outcomes will be measured at Visit 1 Commencement, Visit 2 (halfway: 6 weeks after commencement) and Visit 3 (Primary timepoints: 12 weeks after commencement) .
Secondary outcome [2] 416843 0
2. Impact of pain as measured by BPI, PCS and PSEQ
Timepoint [2] 416843 0
Outcomes will be measured at Visit 1 Commencement, Visit 2 (halfway: 6 weeks after commencement) and Visit 3 (Primary timepoints: 12 weeks after commencement) .
Secondary outcome [3] 416844 0
3. Levels of depression as measured by DASS-21
Timepoint [3] 416844 0
Outcomes will be measured at Visit 1 Commencement, Visit 2 (halfway: 6 weeks after commencement) and Visit 3 (Primary timepoints: 12 weeks after commencement) .
Secondary outcome [4] 416845 0
4. Level of anxiety as measured by DASS-21
Timepoint [4] 416845 0
Outcomes will be measured at Visit 1 Commencement, Visit 2 (halfway: 6 weeks after commencement) and Visit 3 (Primary timepoints: 12 weeks after commencement) .
Secondary outcome [5] 416846 0
5. Level of stress as measured by DASS-21
Timepoint [5] 416846 0
Outcomes will be measured at Visit 1 Commencement, Visit 2 (halfway: 6 weeks after commencement) and Visit 3 (Primary timepoints: 12 weeks after commencement) .
Secondary outcome [6] 416847 0
6. GROC: Global Rating of Change
Timepoint [6] 416847 0
Outcomes will be measured at Visit 1 Commencement, Visit 2 (halfway: 6 weeks after commencement) and Visit 3 (Primary timepoints: 12 weeks after commencement) .

Eligibility
Key inclusion criteria
a) at least 18 years old;
b) diagnosis of FMS according to ACR 2011 criteria by a pain specialist or rheumatologist
c) oral morphine equivalent daily dose (OMEDD) less than 60mg;
d) provision of written informed consent;
e) able to complete questionnaires.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
f) current treatment with naltrexone;
g) severe medical or psychiatric illness likely to limit life or participation in trial;
h) pregnant or planning pregnancy during study period;
i) known allergy to naltrexone or naloxone;
j) currently participating in other clinical trials.

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)
Placebo and drug coded.
Codes randomised to recruited cohort via drawing of blank envelope.
Code known only to dispensing pharmacy - until point of statistical analysis.
Medications will be dispensed in bottles with 7 capsules in each bottle. Bottles will be marked numerically 1-12 according to the week in which those capsules are to be taken. There will be no discernible difference between the placebo and active capsules and bottles.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation
Batches of medication and placebo will be grouped into 10 patient allocations (5 beginning with treatment, 5 beginning with placebo) by pharmacy staff. These will be assigned a code by random number generation and these medication codes will be assigned via random choice of 10 blind envelopes (drawn by pharmacy staff) to beginning with treatment or beginning with control. Medication codes will be put into 10 separate envelopes, which will then be given by the clinician to the patient. Patients will bring the medication code to the pharmacy to pick up the corresponding medication. All randomisation and blinding will be completed by the pharmacy team and kept in a separate database away from clinical staff and research team, thus ensuring double blinding (both clinician and patient). Sequence generation of the randomised period to beginning or end of the treatment will be through batch randomisation of 10 participants at a time through blind draw of 10 blind envelopes as above.
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
Intervention assignment
Crossover
Other design features
12-week single-centre, prospective, randomised double-blinded, placebo-controlled trial with a crossover design using a 4-week control period, which is randomly allocated to each patient to either precede or follow the 8-week active drug period, thus creating a 12-week study. The placebo period is always 4 weeks duration and the treatment period is always 8 weeks duration (including 2-week ramp of dose). This crossover method was decided on after consultation with the biostatistics team, in order to gain adequate power from the sample size of approximately 80 people that we are likely to be able to recruit.
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis
Primary outcome analysis will be based on the estimation of between-group differences in measurements after 8 weeks of treatment and 4 weeks of placebo (control) for the primary outcome. Data analyses will be performed following an intention-to-treat plan and differences will be calculated using the student t-test. Power analysis was performed by UQ biostatistics with a 0.8 power at p=0.05, giving a sample size of 77. Expert statistical input will sought for in-depth analysis of secondary outcomes using regression analysis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2023
Actual
Date of last participant enrolment
Anticipated
1/05/2024
Actual
Date of last data collection
Anticipated
1/09/2024
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 23692 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 39127 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 312769 0
Hospital
Name [1] 312769 0
Metro South Hospital and Health service
Country [1] 312769 0
Australia
Funding source category [2] 312825 0
University
Name [2] 312825 0
University of Queensland
Country [2] 312825 0
Australia
Primary sponsor type
Hospital
Name
Metro South Hospital and Health service
Address
Metro South Pain and Rehabilitation Centre
Burke Street Centre
Building 2, 2 Burke St
Woolloongabba 4102 QLD
Country
Australia
Secondary sponsor category [1] 314399 0
University
Name [1] 314399 0
University of Queensland
Address [1] 314399 0
University of Queensland
School of Pharmacy
Pharmacy Australia Centre of Excellence
20 Cornwall St, Woolloongabba
QLD 4102
Country [1] 314399 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312066 0
Metro South Hospital and Health Service Human Research Ethics Committee (EC00167)
Ethics committee address [1] 312066 0
Administrator: Shona Van Garderen
Chair: Dr Mary Boyde
Level 7, Translational Research Institute Building
Princess Alexandra Hospital
Ipswich Road, Woolloongabba Qld 4102
Ethics committee country [1] 312066 0
Australia
Date submitted for ethics approval [1] 312066 0
18/01/2023
Approval date [1] 312066 0
Ethics approval number [1] 312066 0

Summary
Brief summary
Preliminary evidence shows that low-dose naltrexone (LDN) has a clinically beneficial impact on fibromyalgia pain, function and quality of life. However, only a few small clinical trials with high risk of bias have investigated the effect of LDN on fibromyalgia symptoms. The primary aim of this double-blind, randomised, controlled trial is to evaluate the efficacy of LDN in reducing pain in patients with fibromyalgia over a 12-week period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123342 0
Dr Nicholas Aitcheson
Address 123342 0
Metro South Pain and Rehabilitation Centre.
2 Burke St
Woolloongabba
QLD
4102
Country 123342 0
Australia
Phone 123342 0
+61 731761901
Fax 123342 0
Email 123342 0
[email protected]
Contact person for public queries
Name 123343 0
Dr Nicholas Aitcheson
Address 123343 0
Metro South Pain and Rehabilitation Centre.
2 Burke St
Woolloongabba
QLD
4102
Country 123343 0
Australia
Phone 123343 0
+61 731761901
Fax 123343 0
Email 123343 0
[email protected]
Contact person for scientific queries
Name 123344 0
Dr Nicholas Aitcheson
Address 123344 0
Metro South Pain and Rehabilitation Centre.
2 Burke St
Woolloongabba
QLD
4102
Country 123344 0
Australia
Phone 123344 0
+61 731761901
Fax 123344 0
Email 123344 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Deidentified demographic data
Deidentified baseline and outcome measurement data
When will data be available (start and end dates)?
01/03/2025 - 01/03/2035
Available to whom?
Fibromyalgia/LDN researchers, on request from principle investigator
Available for what types of analyses?
Repeat analysis of primary data
Meta-analysis
How or where can data be obtained?
On request from PI.
Dr Nicholas Aicheson
[email protected]
Data will be stored in the University of Queensland Data Bank.


What supporting documents are/will be available?

Current supporting documents:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17744Study protocol    385071-(Uploaded-30-11-2022-13-35-21)-Study-related document.docx


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17744Study protocol    385071-(Uploaded-18-01-2024-15-50-51)-Study-related document.docx

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.