Fibromyalgia and Naltrexone: The FINAL Study

Odense University Hospital

Status and phase: Completed; Phase 2

Conditions: Fibromyalgia

Treatments: Drug: Placebo oral tablet; Drug: Naltrexone Pill

Study type: Interventional

Funder types: Other

Identifiers

NCT04270877

2019-000702-30 (EudraCT Number)

18021

A3650 (Other Grant/Funding Number)

R177-A6158 (Other Grant/Funding Number)

21-10-0037 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

Low dose naltrexone (LDN) is used widely as off label treatment in patients with fibromyalgia, despite the lack of larger randomized controlled trials (RCT) supporting an effect.

LDN has antagonistic effect on both opioid receptors and on toll-like receptors in glia cells. Mediated via those receptors, LDN can potentially reduce neuroinflammation and induce homeostasis in the endorphin system in patients with fibromyalgia.

The aim of the trial is to investigate whether treatment with LDN has a superior effect compared to placebo on pain among female patients with fibromyalgia, evaluated after 12 weeks of treatment. The study is also exploring secondary aims regarding a possible improvement of other fibromyalgia core symptoms and a possible improvement of global assessment, daily functioning and health-related quality of life. Among the exploratory secondary objectives are changes in muscle exhaustion, physical fitness, pain sensitivity, inhibition of pain, augmentation of pain, and pro-inflammatory cytokines.

Enrollment: 99 patients

Sex: Female

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• Known allergy against naltrexonehydroclorid
• Pregnancy or breastfeeding. A negative pregnancy test has to be available for all fertile subjects at baseline
• Use of opioids or NSAIDs during the 4 weeks before inclusion in the trial
• 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")

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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99 participants in 2 patient groups, including a placebo group

Naltrexone

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone Pill

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo oral tablet