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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12623000172606
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
7/12/2022
Date registered
Help: Date registered
20/02/2023
Date last updated
Help: Date last updated
17/08/2026
Date data sharing statement initially provided
Help: Data sharing statement date
20/02/2023
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
Low Dose Naltrexone in Fibromyalgia - A randomised controlled cross-over trial
Scientific title
Low dose naltrexone in fibromyalgia: a double-blind randomised placebo-controlled 12-week, two-period, two-sequence Phase 2 cross-over trial
Additional trial identifiers [1] 308528 0
LDN-AU-UQ-001
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(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 the intervention or 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
Description of the comparator or control
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). Take one capsule one hour before bedtime at night.
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) male or female, greater than or equal to 18, and less than or equal to 65 years of age.
b) diagnosis of FMS according to the American College of Rheumatology (ACR) 2010 criteria utilising the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) by a pain specialist or rheumatologist
c) oral morphine equivalent daily dose (OMEDD) less than 60mg at least 4 weeks prior to study participation

* If participants require a total dose more than 60 mg OMEDD, they can continue taking LDN throughout operations or acute pain flares because LDN is an antagonist of only a very small percentage of opioid receptors. The effect on opioid analgesia is minimal. We do not suggest altering the LDN dose as opioids are introduced or withdrawn.
** Male participants should use condoms and abstain from donating sperm from screening until 2 weeks after last dose of naltrexone.
d) agree to maintain oral morphine equivalent daily dose (OMEDD) less than 60 mg for the duration of the trial*
e) provision of written informed consent
f) able to complete questionnaires
g) Male participants with female sexual partners who are women of childbearing potential must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods**
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
h) current treatment with naltrexone
i) severe medical or psychiatric illness likely to limit life or participation in trial
j) pregnant participants or planning pregnancy during study period***
k) known allergy to naltrexone or naloxone
l) currently participating in an interventional clinical trial or has participated in another clinical study within the last four weeks or within five half-lives of the prior study treatment, whichever is longer
m) a history of acute hepatitis or liver failure or hepatic impairment
n) a history of severe renal impairment
o) evidence of joint inflammation or any history of rheumatic or autoimmune disease

*** Women of child-bearing potential (WOCBP) must confirm that they are not pregnant at enrolment prior to randomisation. They must use a highly effective contraceptive method including oral contraceptive pills [OCPs], or an intrauterine hormone device [IUD]) from screening until 2 weeks after last dose of naltrexone. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle do not need to use contraception.

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)
As each participant is confirmed eligible for the study, they will be allocated a participant number, starting from 01 and taking the next available participant code. The participant and the investigators will keep a record of the participant number. The investigators will provide the participant’s name and number, and instructions to dispense the trial medication for the participant, in the form of a prescription to the compounding pharmacy.

The compounding pharmacy will create a randomisation schedule in which participant numbers are allocated to Group 1 or Group 2 in the ratio 1:1 in blocks of 10, i.e. five to Group 1 and five in Group 2 within each block of 10 participants, using random number generation. This change to sequence generation was created prior to recruitment of any participants.
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 2
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
Recruiting
Date of first participant enrolment
Anticipated
1/11/2024
Actual
1/11/2024
Date of last participant enrolment
Anticipated
31/12/2026
Actual
Date of last data collection
Anticipated
1/03/2027
Actual
Sample size
Target
90
Accrual to date
35
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
University
Name
The University of Queensland
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
Hospital
Name [1] 314399 0
Metro South Hospital and Health service
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
Approved
Ethics committee name [1] 312066 0
Metro South Hospital and Health Service Human Research Ethics Committee (EC00167)
Ethics committee address [1] 312066 0
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
Ethics committee name [2] 321209 0
The University of Queensland
Ethics committee address [2] 321209 0
Ethics committee country [2] 321209 0
Australia
Date submitted for ethics approval [2] 321209 0
11/12/2023
Approval date [2] 321209 0
18/01/2024
Ethics approval number [2] 321209 0
2023/HE001923

Summary
Brief summary
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
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
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 the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Fibromyalgia/LDN researchers, on request from principle investigator

Conditions for requesting access:
• -

What individual participant data might be shared?
• Deidentified demographic data
Deidentified baseline and outcome measurement data


What types of analyses could be done with individual participant data?
• Repeat analysis of primary data
Meta-analysis

When can requests for individual participant data be made (start and end dates)?
From:
01/03/2025

To:
01/03/2035

Where can requests to access individual participant data be made, or data be obtained directly?
• On request from PI.
Dr Nicholas Aicheson
[email protected]
Data will be stored in the University of Queensland Data Bank.

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol    Research Procotol_ LDN Fibromyalgia_V1.5_22092023_clean.pdf


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.