Fibromyalgia and Naltrexone: The FINAL Study

NCT04270877 | Completed Phase 2 DMC

• 5 other identifiers: 180212019-000702-30R177-A6158A365021-10-0037
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effect of low dose naltrexone (LDN) on pain in women with fibromyalgia (FM). The study is designed as a parallel randomized (1:1) double blind, placebo-controlled superiority trial. Half of the participants will receive treatment with LDN while the other half will receive treatment with placebo.

Conditions

Fibromyalgia

Outcome Measures

Primary Outcomes (1)

• Average pain during the last 7 days

  Assessed by asking the participants about the level of average pain during the last 7 days on a 11 point rating scale, ranging from 0-10 (0 = "no pain" and 10 = "unbearable pain") using the first item from the symptom part of the Fibromyalgia Impact Questionnaire Revised. A lower score indicates lower severity.

  Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo

Secondary Outcomes (21)

• Global assessment

  Change in overall fibromyalgia symptoms from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo

• Impact of fibromyalgia

  Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo

• Pain distribution

  Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo

• Level of pain

  Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo

• Level of tenderness

  Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo

Other Outcomes (6)

• Variation in pain

  Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo

• Muscle exhaustion

  Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo

• Physical fitness

  Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo

Study Arms (2)

Naltrexone

EXPERIMENTAL

Low Dose Naltrexone (LDN) is administered for 12 weeks, including a titration phase of 4 weeks. Participants will be titrated up to 6 mg following a dose escalation scheme: Initial dosage of 1.5 mg daily, escalated every seventh day by 1.5 mg up to 6 mg at week 4. Dose escalation will be based on safety and tolerability, and if dose escalation is not feasible, delayed increments are allowed. After end of titration (week 4) the subjects will be maintained at the highest tolerated dose level for the last 8 weeks of the treatment period. Subjects are not allowed to change dose during the last 8 weeks of the treatment period. The medicine is taken orally as tablets once daily in the evening.

Drug: Naltrexone Pill

Placebo

PLACEBO COMPARATOR

LDN-placebo is administered for 12 weeks, including a titration phase of 4 weeks. Participants will be titrated up to 6 mg following a dose escalation scheme: Initial dosage of 1.5 mg daily, escalated every seventh day by 1.5 mg up to 6 mg at week 4. Dose escalation will be based on safety and tolerability, and if dose escalation is not feasible, delayed increments are allowed. After end of titration (week 4) the subjects will be maintained at the highest tolerated dose level for the last 8 weeks of the treatment period. Subjects are not allowed to change dose during the last 8 weeks of the treatment period. The medicine is taken orally as tablets (similar in size, shape and taste to the active medication), once daily in the evening.

Drug: Placebo oral tablet

Interventions

Naltrexone Pill DRUG

Treatment with LDN for 12 weeks, including af titration phase of 4 weeks. Initial dosage of 1.5 mg, dose is increased by 1.5 mg every 7th day to 6 mg at week 4. Dosing is increased based on safety and tolerability and delayed increments are allowed. The participants are maintained on the highest tolerable dose for the last 8 weeks of the treatment period.

Also known as: LDN

Naltrexone

Placebo oral tablet DRUG

Treatment with LDN-placebo for 12 weeks, including af titration phase of 4 weeks. Initial dosage of 1.5 mg, dose is increased by 1.5 mg every 7th day to 6 mg at week 4. Dosing is increased based on safety and tolerability and delayed increments are allowed. The participants are maintained on the highest tolerable dose for the last 8 weeks of the treatment period.

Also known as: LDN-placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18-64 years
• Understands and writes Danish
• Fulfills the American College of Rheumatology 1990 criteria for fibromyalgia
• A minimum score of 4 in self-reported average pain during the last 7 days on a 0-10 numeric rating scale at baseline
• All fertile women have to use safe anti conception (Spiral, birth control pills, contraceptive patch, contraceptive vaginal ring or gestagen injections) for 3 weeks before and 1 week after the trial. If the patients' normal lifestyle includes sexual abstinence, they do not have to use anti conception. Instead they can give an oral informed consent, that they will be sexually abstinent during the trial. A woman is considered non-fertile if she is sterilized, hysterectomized, bilateral oophorectomized or is postmenopausal. A woman is considered postmenopausal when vaginal bleeding has been absent for 1 year and is confirmed by measurement of follicle-stimulating hormone.

You may not qualify if:

• Known allergy against naltrexonehydroclorid
• Pregnancy or breastfeeding. A negative pregnancy test has to be available for all fertile subjects at baseline
• Abuse of alcohol or other substances
• Inflammatory rheumatic diseases
• Demyelinating diseases
• Active cancer
• Liver dysfunction
• Kidney dysfunction
• Psychotic diseases
• History of suicide attempts
• Suicide ideation - evaluated using Patient Health Questionnaire-9 (Item 9 has to be answered "never")

Sponsors & Collaborators

• Odense University Hospital: lead
• University of Southern Denmark: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator

Study Sites (1)

Pain centre, Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (2)

• Due Bruun K, Christensen R, Amris K, Vaegter HB, Blichfeldt-Eckhardt MR, Bye-Moller L, Holsgaard-Larsen A, Toft P. Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2024 Jan;6(1):e31-e39. doi: 10.1016/S2665-9913(23)00278-3. Epub 2023 Dec 5.

  PMID: 38258677 DERIVED

• Bruun KD, Amris K, Vaegter HB, Blichfeldt-Eckhardt MR, Holsgaard-Larsen A, Christensen R, Toft P. Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial. Trials. 2021 Nov 15;22(1):804. doi: 10.1186/s13063-021-05776-7.

  PMID: 34781989 DERIVED

MeSH Terms

Conditions

Fibromyalgia

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Karin D Bruun, Consultant

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A parallel randomized (1:1) double blind, placebo-controlled superior trial

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: February 17, 2020
• Study Start: January 6, 2021
• Primary Completion: December 27, 2022
• Study Completion: December 27, 2022
• Last Updated: December 29, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)