12-month Randomized, Double-blind, Placebo-controlled, Pharmacological Clinical Trial to Evaluate the Effectiveness, Cost-utility and Neurobiological Effects of Low-dose Naltrexone in Patients With Fibromyalgia (INNOVA Project)

ICI20/00080

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.

2022-06-01

2024-10-31

2024-12-31

Active (not recruiting)

Early phase I

99

General Inclusion Criteria: * Female between 18 and 70 years old * Patients diagnosed of FM according to ACR 2016 criteria * Chronic widespread pain for at least 6 months ranked ≥ 4 out of 10; * Understand Spanish; * Written informed written consent; General Exclusion Criteria: * Treatment with opiates in last 3 months; * Diagnosis of severe medical/psychiatric disorders (e.g. cancer, severe depression, psychotic disorder, schizophrenia); * Being pregnant (or planning a pregnancy during the study period) or breastfeeding; * Known allergy to naltrexone or naloxone; * Hematological disorders; * Abnormal hepatic function; * Taking anticoagulant medication; * Alcohol consume during the study period * Participation in other clinical trials; Additional inclusion criteria for biomarker sub-study: Right-handed (for the neuroimaging tests) Additional exclusion criteria for biomarker sub-study: Comorbid rheumatologic illnesses (e.g. rheumatoid arthritis, lupus); fever (\> 38ºC) or infection in the last 2 weeks; vaccination in the last 4 weeks; Take drugs with anti-inflammatory effects in the 72h prior to blood / neuroimaging; taking cortisone or anti-cytokine therapy; needle phobia; inability to be scanned (due to claustrophobia, metal implants, pacemakers, etc.); Body Mass Index (BMI) \> 36 kg/m2; consumption of \> 8 units of caffeine per day; smoking \> 10 cigarettes/day; acute pain not-related to FM on the day of the scan (e.g. headache, back pain).

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Double-blind, randomized controlled trial', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 99, 'type': 'ACTUAL'}}

2024-04-22