NCT04739995: INNOVA

Cost-utility and Physiological Effects of LDN in Patients With Fibromyalgia

Active, enrolled Phase 4 Last updated 22 April 2024

What this trial tests

Phase 4 trial testing Low-dose naltrexone in Randomized Controlled Trial in 99 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

1 June 2022

Primary endpoint
31 October 2024

31 December 2024

Quick facts

Lead sponsor	Fundació Sant Joan de Déu
Phase	Phase 4
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	99
Start date	1 June 2022
Primary completion	31 October 2024
Estimated completion	31 December 2024
Sites	1 location across Spain

Drugs / interventions tested

• Low-dose naltrexone

Conditions studied

• Randomized Controlled Trial — all drugs for Randomized Controlled Trial →

Sponsor

Fundació Sant Joan de Déu — full company profile →

Who can join

Adults 18 to 70, female only, with Randomized Controlled Trial. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background: Low-dose naltrexone (LDN) may be useful in managing the pathologies that alter inflammatory markers, such as Crohn's disease or fibromyalgia (FM). The anti-inflammatory effect of LDN should be produced through the inhibition of Toll-like receptor 4 activity expressed in the membrane of various immune system cells (e.g. microglia). Conversely, due to a rebound effect, LDN could exercise an analgesic effect that strengthens the endogenous inhibitory system. According to this hypothesis, the low-intensity and intermittent blocking of the opioid receptors generated by LDN should induce a compensatory mechanism that should facilitate an increase in the production of endogenous opioids and greater sensitivity of the system to their effects. To date, the effects of LDN in patients with FM have been evaluated through crossover studies that have yielded promising results. Given that the studies conducted up to now have had small sample sizes and crossover designs, and given that there are still no studies in which its potential cost-utility is assessed, studies with greater methodological rigor and larger samples are necessary to confirm the effectiveness of LDN in FM.

Jointly evaluating the effectiveness and cost-utility, the changes in metabolites in certain areas of the brain, and systemic inflammatory markers potentially linked to the etiopathogenesis of FM, should allow us to gain a more detailed knowledge of the neurobiological mechanisms underlying the effectiveness of LDN in this population.

Objectives: To evaluate the effectiveness and safety of LDN in patients with FM and analyse its cost-utility both from the government and the healthcare perspective at 1-year follow-up. Brain metabolites and systemic inflammatory biomarkers will be included to evaluate neurobiological mechanisms behind LDN therapeutic effects.

Design: Randomized, Controlled Trial. Centre: Parc Sanitari Sant Joan de Déu (St. Boi de Llobregat, Spain). Participants: 120 patients with FM will be randomly assigned to LDN (4.5mg/day) or placebo.

Main outcome measure: Pain severity using Ecological Momentary Assessment. Secondary outcomes: functionality, affective symptoms, fibrofog, quality of life. Costs and QALYs will be also calculated. Biomarkers: 50% of the patients will be scanned at baseline and at week 12 for changes in brain metabolites related to neuroinflammation and central sensitization. Immune-inflammatory markers in serum will also be evaluated.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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).
   Colomer-Carbonell A, Sanabria-Mazo JP, Hernández-Negrín H, Borràs X, et al · · 2022 · cited 6× · PMID 34992118 · DOI 10.1136/bmjopen-2021-055351
2. Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.
   Guo X, Liu H, Song YJ, Wang JH, et al · · 2026 · cited 2× · PMID 41583906 · DOI 10.1002/mco2.70497
3. Low-Dose Naltrexone in Chronic Pain Management: Mechanisms, Evidence, and Clinical Implications.
   McKenzie A, Bittar T, Dombrower R, Raman D, et al · · 2026 · PMID 41893019 · DOI 10.3390/jpm16030151