Clinical trial NCT04270877: Fibromyalgia and Naltrexone: The FINAL Study
Official title: Fibromyalgia and Naltrexone: The FINAL Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fibromyalgia
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: University of Southern Denmark
name: University Hospital Bispebjerg and Frederiksberg
First posted: 2020-02-17
Enrollment: 99
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A parallel randomized (1:1) double blind, placebo-controlled superior trial
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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")

Primary outcomes:
measure: Average pain during the last 7 days
timeFrame: Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
Secondary outcomes:
measure: Global assessment
timeFrame: Change in overall fibromyalgia symptoms from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Impact of fibromyalgia
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Pain distribution
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of pain
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of tenderness
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of fatigue
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of sleep disturbance
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of depression
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of anxiety
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of cognition
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of stiffness
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Level of physical function
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Health-related quality of life - mobility
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Health-related quality of life - self care
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Health-related quality of life - usual activities
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Health-related quality of life - pain/discomfort
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Health-related quality of life - anxiety/depression
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Health-related quality of life - global
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Number of responders with a more than 15% improvement of pain
timeFrame: Number of responders after 12 weeks of treatment with LDN or LDN placebo
measure: Number of responders with a more than 30% improvement of pain
timeFrame: Number of responders after 12 weeks of treatment with LDN or LDN placebo
measure: Number of responders with a more than 50% improvement of pain
timeFrame: Number of responders after 12 weeks of treatment with LDN or LDN placebo
Other outcomes:
measure: Variation in pain
timeFrame: Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo
measure: Muscle exhaustion
timeFrame: Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
measure: Physical fitness
timeFrame: Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
measure: Pain sensitivity
timeFrame: Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
measure: Inhibition of pain
timeFrame: Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
measure: Augmentation of pain
timeFrame: Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo
Locations:
city: Odense
country: Denmark
facility: Pain centre, Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Karin D Bruun, Consultant
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.