Study protocol for a randomised, double-blinded, placebo-controlled phase III trial examining the add-on efficacy, cost-utility and neurobiological effects of low-dose naltrexone (LDN) in patients with fibromyalgia (INNOVA study).

Abstract

INTRODUCTION:

There is evidence that low-dose naltrexone (LDN; <5.0 mg/day) reduces pain and improves the quality of life of people with fibromyalgia syndrome (FMS). However, no randomised controlled trials with long-term follow-ups have been carried out. The INNOVA study will evaluate the add-on efficacy, safety, cost-utility and neurobiological effects of LDN for reducing pain in patients with FMS, with a 1-year follow-up.

METHODS AND ANALYSIS:

A single-site, prospective, randomised, double-blinded, placebo-controlled, parallel design phase III trial will be performed. Eligibility criteria include being adult, having a diagnosis of FMS and experiencing pain of 4 or higher on a 10-point numerical rating scale. Participants will be randomised to a LDN intervention group (4.5 mg/day) or to a placebo control group. Clinical assessments will be performed at baseline (T0), 3 months (T1), 6 months (T2) and 12 months (T3). The primary endpoint will be pain intensity. A sample size of 60 patients per study arm (120 in total), as calculated prior to recruitment for sufficient power, will be monitored between January 2022 and August 2024. Assessment will also include daily ecological momentary evaluations of FMS-related symptoms (eg, pain intensity, fatigue and sleep disturbance), and side effects via ecological momentary assessment through the Pain Monitor app during the first 3 months. Costs and quality-adjusted life years will be also calculated. Half of the participants in each arm will be scanned with MRI at T0 and T1 for changes in brain metabolites related to neuroinflammation and central sensitisation. Inflammatory biomarkers in serum will also be measured.

ETHICS AND DISSEMINATION:

This study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and community engagement activities.

TRIAL REGISTRATION NUMBER:

NCT04739995.

• Authors: Ariadna Colomer-Carbonell, Juan P Sanabria-Mazo, Halbert Hernández-Negrín, Xavier Borràs, Carlos Suso-Ribera, Azucena García-Palacios, Jordi Muchart, Josep Munuera, Francesco D'Amico, Michael Maes, Jarred W Younger, Albert Feliu-Soler, Antoni Rozadilla-Sacanell, Juan V Luciano
• Journal: BMJ open (BMJ Open) Vol. 12 Issue 1 Pg. e055351 (Jan 06 2022) ISSN: 2044-6055 [Electronic] England
• PMID: 34992118 (Publication Type: Clinical Trial Protocol, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Naltrexone

Topics

• Adult
• Clinical Trials, Phase III as Topic
• Double-Blind Method
• Fibromyalgia (drug therapy)
• Humans
• Naltrexone (therapeutic use)
• Prospective Studies
• Quality of Life
• Randomized Controlled Trials as Topic