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

NCT04739995 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: ICI20/00080
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Pain intensity

  -Numerical Rating Scale-NRS- from 0 (no pain) to 10 (worst possible pain)

  Through study completion, an average of 1 year

Secondary Outcomes (3)

• Revised Fibromyalgia Impact Questionnaire (FIQR)

  Through study completion, an average of 1 year

• Depression Anxiety Stress Scale (DASS-21)

  Through study completion, an average of 1 year

• Multidimensional Inventory of Subjective Cognitive Impairment (MISCI)

  Through study completion, an average of 1 year

Other Outcomes (9)

• EuroQoL (EQ-5D-5L)

  Through study completion, an average of 1 year

• Client Service Receipt Inventory (CSRI)

  Through study completion, an average of 1 year

• Patient Global and Specific Impression of Change (PGIC/PSIC)

  Through study completion, an average of 1 year

Study Arms (2)

Low-Dose-Naltrexone (LDN)

EXPERIMENTAL

The LDN treatment will consist of one 4.5 mg naltrexone tablet (lactose-free) taken daily for 12 months before going to sleep.

Drug: Low-dose naltrexone

Placebo

PLACEBO COMPARATOR

The control group will take the placebo daily (a film-coated tablet, identical to the LDN, filled with a lactose-free excipient), for 12 months, following the same guidelines.

Drug: Low-dose naltrexone

Interventions

Low-dose naltrexone DRUG

4.5 mg LDN/day for 1 year

Also known as: LDN

Low-Dose-Naltrexone (LDN); Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;
• Right-handed (for the neuroimaging tests)
• 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).

Sponsors & Collaborators

• Fundació Sant Joan de Déu: lead
• Carlos III Health Institute: collaborator

Study Sites (1)

Parc Sanitari Sant Joan de Déu (PSSJD)

Sant Boi de Llobregat, Barcelona, 08830, Spain

Location

Related Publications (1)

• Colomer-Carbonell A, Sanabria-Mazo JP, Hernandez-Negrin H, Borras X, Suso-Ribera C, Garcia-Palacios A, Muchart J, Munuera J, D'Amico F, Maes M, Younger JW, Feliu-Soler A, Rozadilla-Sacanell A, Luciano JV. 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). BMJ Open. 2022 Jan 6;12(1):e055351. doi: 10.1136/bmjopen-2021-055351.

  PMID: 34992118 DERIVED

MeSH Terms

Interventions

Naltrexone

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Juan V. Luciano, PhD

  Fundació Sant Joan de Déu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized controlled trial

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 5, 2021
• Study Start: June 1, 2022
• Primary Completion: October 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 22, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)