Low-dose Naltrexone for Post-COVID Fatigue Syndrome

NCT05430152 | Completed Phase 2 DMC

• 1 other identifier: H21-02254
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine if low-dose naltrexone (LDN) reduces fatigue, improves related symptoms, and reduces inflammatory markers in peripheral blood in cases with Post-COVID-19 Fatigue Syndrome (PCFS) from COVID-19 (i.e. confirmed SARS-CoV-2 case). LDN refers to naltrexone given in doses of 1-4.5 mg. Overall, studies have found that LDN is safe and well-tolerated. It may help to reduce pain and inflammation and improve well-being and immune function.The trial will be conducted by the Complex Chronic Diseases Program (CCDP) at BC Women's Hospital and will demonstrate whether LDN could benefit a large number of people with PCFS.

Conditions

Post-Viral Fatigue Syndrome

Keywords

Post-COVID Fatigue Syndrome; Long-COVID; COVID-19; SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• Fatigue Intensity

  Change in the Fatigue Severity Scale (FSS) total score by 4.7 points or over

  16 weeks

Secondary Outcomes (4)

• Pain Severity

  16 weeks

• Symptom Severity

  16 weeks

• Activity Levels

  16 weeks

• Self-reported Quality of Life

  16 weeks

Other Outcomes (15)

• Exploratory outcome: Changes in inflammatory marker values in peripheral blood

  16 weeks

• Exploratory outcome: Disease Severity

  16 weeks

• Exploratory outcome: Reverse triiodothyronine (rT3) profile (as an indirect marker of disease severity)

  16 weeks

Study Arms (2)

Low-Dose Naltrexone

EXPERIMENTAL

The Low-Dose Naltrexone (LDN) will be provided as a compounded capsule starting at a strength of 1mg/day of naltrexone and increasing up to a maximum of 4.5 mg/day. The compounding pharmacy will compound the needed doses in Capsugel® empty gelatin based capsules using Naltrexone Hydrochloride Tablets and CELLULOSE.

Drug: Low-Dose Naltrexone

Placebo

PLACEBO COMPARATOR

Matching placebo capsule will be created by compounding pharmacy to look exactly like the LDN doses. The compounding pharmacy will compound the placebo in Capsugel® empty gelatin based capsules using CELLULOSE.

Other: Placebo

Interventions

Placebo OTHER

Study drug dosing schedule (Placebo; capsules made to match LDN doses): * Week 1: 1 mg/day (1 mg cap) * Week 2: 2 mg/day (two 1 mg caps) * Week 3: 3 mg/day (three 1mg caps) * Weeks 4-6: 4.5 mg/day (three 1 mg caps, plus one 1.5 mg cap = 4.5 mg/day) * Weeks 7-16: 4.5 mg/day (one 4.5 mg cap) OR based on self-titration dosage (one 1mg, 2mg, or 3mg cap)

Placebo

Low-Dose Naltrexone DRUG

Study drug dosing schedule (LDN): * Week 1: 1 mg/day (1 mg cap) * Week 2: 2 mg/day (two 1 mg caps) * Week 3: 3 mg/day (three 1mg caps) * Weeks 4-6: 4.5 mg/day (three 1 mg caps, plus one 1.5 mg cap = 4.5 mg/day) * Weeks 7-16: 4.5 mg/day (one 4.5 mg cap) OR based on self-titration dosage (one 1mg, 2mg, or 3mg cap)

Also known as: LDN

Low-Dose Naltrexone

Eligibility Criteria

• Age: 19 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients ages 19 to less than 70 years
• Case of SARS-CoV-2 over 3 previously, confirmed by a positive test result or clinical confirmation by a physician
• Meet the clinical diagnostic criteria for PCFS
• Agree to maintain any other regular medications at current doses for the duration of the trial (except for essential need of new medication or dose change, as prescribed by a physician)
• Agree to use effective contraception for the trial duration, as appropriate, if female.
• The participant resides within the delivery area for the drug as determined by FedEx Clinical Trial Services

You may not qualify if:

• Pregnant, planning to become pregnant, or breastfeeding
• Opioid medications:
• Any use within last 15 days, as reported by the patient
• During the trial
• A positive urine test for opioids (only for the first 16 participants)
• History of alcohol, opioid or other substance misuse
• Participation in another interventional clinical trial in the last 30 days or planned during the trial period
• Confirmed ME/CFS or FM existing prior to SARS-CoV-2 infection
• Allergy to naltrexone or medication components
• Acute hepatitis, liver failure, or severe kidney failure.
• Current or recent use of naltrexone in the last 30 days
• The participant is not an ideal candidate for the study, in the opinion of the investigator, for any other reason (ie. personal or logistic, medication, condition, etc.) that could impact the participant's safety or the results of the study.
• Opioid Washout Period:
• Potential participants who are currently taking opioid medications who wish to enrol the study will be instructed they can stop taking opioid medications for 15 days before continuing the screening process. They will be instructed that they should speak with their family doctor before stopping any prescribed medications.
• Positive Urine Test for Opioids:

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR): collaborator
• Women's Health Research Institute of British Columbia: collaborator
• Luis Nacul: lead
• University of British Columbia: collaborator
• Provincial Health Services Authority British Columbia: collaborator

Study Sites (1)

Women's Health Research Institute

Vancouver, British Columbia, V6H 3N1, Canada

Location

Related Publications (1)

• Naik H, Cooke E, Boulter T, Dyer R, Bone JN, Tsai M, Cristobal J, McKay RJ, Song X, Nacul L. Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia. BMJ Open. 2024 May 13;14(5):e085272. doi: 10.1136/bmjopen-2024-085272.

  PMID: 38740499 DERIVED

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Post-Acute COVID-19 Syndrome; COVID-19

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders

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

• Luis Nacul, MD, PhD

  WHRI / University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded placebo-controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: Randomized parallel group double-blinded placebo-controlled trial

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 24, 2022
• Study Start: January 15, 2024
• Primary Completion: February 15, 2026
• Study Completion: February 28, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Protocol has been shared in peer-reviewed paper
• Access Criteria: open access

Locations

CA (1)