Low dose naltrexone for the treatment of fibromyalgia: Protocol for a double-blind, randomized, placebo-controlled trial

Abstract

\n Background Low dose naltrexone (LDN) is used widely as off-label treatment for pain despite limited evidence for its effectiveness. A few small trials with high risk of bias have investigated the effect of LDN on pain associated with fibromyalgia in women, but larger and more methodologically robust studies are needed. The primary aim of this randomized controlled trial is to investigate if 12 weeks of LDN treatment is superior to placebo in reducing the average pain intensity during the last seven days in women with fibromyalgia.Methods A single-center, permuted block randomized, double-blind, placebo-controlled, parallel-group trial will be performed in Denmark. Randomization comprises 100 women aged 18–64 years and diagnosed with fibromyalgia who will be treated with either LDN or placebo for 12 weeks including a four-week titration phase. The primary outcome is change in average pain intensity (during the last seven days) from baseline to 12 weeks. Secondary outcomes are other fibromyalgia-related symptoms, i.e. tenderness, fatigue, sleep disturbance, stiffness, memory problems, depression, anxiety and measures of global assessment, physical function, impact of fibromyalgia, pain distribution, and health-related quality of life. Intention-to-treat analysis will be performed, and the number of responders with a more than 15%, 30%, and 50% improvement of pain after 12 weeks will be calculated for the LDN and placebo groups. Exploratory outcomes include measures of pain sensitivity, muscle performance, and biomarkers.Discussion This study will contribute with high-level evidence on the efficacy of low dose naltrexone for the treatment of pain in women with fibromyalgia. Secondary outcomes include both disease-specific and generic components investigating whether LDN influences other symptoms than pain. Explorative outcomes are included to provide greater insight into the mechanism of action of LDN and possibly a better understanding of the underlying pathology in fibromyalgia.Trial registration: EudraCT number 2019-000702-30 (registered on 2019-07-12). ClincalTrials.gov Identifier: NCT04270877 (registered on 2020-02-17).