NCT05430152

Low-dose Naltrexone for Post-COVID Fatigue Syndrome

A Double Blind Randomized Trial of Low-dose Naltrexone for Post-COVID Fatigue Syndrome

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (actual)
• Sponsor: Luis Nacul · Academic / Other
• Sex: All
• Age: 19 Years – 69 Years
• Healthy volunteers: Not accepted

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.

Detailed description

There is a growing number of individuals who do not recover to previous levels of health and function following an acute infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but rather develop what has been referred to as 'Long-COVID'. Long-COVID is believed to be multi-causal, with a significant proportion of Long-COVID cases developing a clinical picture indistinguishable from myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) or post-viral fatigue syndrome (PVFS), which we will refer to as post-COVID-19 fatigue syndrome (PCFS). It is characterized by persistent disabling fatigue and other symptoms, such as nonrestorative sleep and post-exertional malaise. Diagnosis is clinical and based on symptom reports owing to the absence of diagnostic biomarkers. Viral and other infections are 25 times more likely to trigger ME/CFS than any other factors. This highlights the possibility of COVID-19 survivors having post-viral symptoms which progress to PCFS, either as the only sequelae or combined with other dysfunctions. Other Long-COVID symptom profiles in addition to PCFS include: a) post-intensive care syndrome; b) organ damage; and c) other debilitating symptoms related to mental health and other conditions. There is no evidence-based treatment for PVFS, however, low-dose naltrexone (LDN), i.e. in doses up to 4.5 mg/day, has been used with some success in cases not related to COVID-19, due to its potential anti-inflammatory, analgesic properties and other mechanisms, targeting potential key mechanisms involved in the development of PVFS and the persistence of symptoms long-term. Previous literature has demonstrated the safety and effectiveness of LDN in other chronic conditions, such as fibromyalgia (FM). The use of LDN as an off label treatment for fibromyalgia and myalgic encephalomyelitis has been used extensively within the BC Women's Hospital + Health Center's Complex Chronic Diseases Program (CCDP) to treat symptoms of pain and fatigue in these clinical populations. The experience of doctors in the CCDP in administering LDN as a medication for these related diseases follows international clinical experience with LDN and the recommended usage from clinical trials in fibromyalgia. Naltrexone is an opiate antagonist approved by Health Canada for treatment for alcohol and opiate use disorders. It is used off label at low doses for conditions such as ME/CFS, fibromyalgia and Crohn's disease, with good safety profile and some evidence of benefit. The impact the COVID-19 pandemic makes finding evidence for an effective and safe treatment for PCFS urgent. With currently no curative treatment for ME/CFS or PCFS, a larger number of people are predicted to be impacted by the long-term morbidity and disability associated with these conditions, with high costs to healthcare and social services. The Double Blind Randomized Trial of Low-Dose Naltrexone for Post-COVID Fatigue Syndrome (PCFS) is a randomized parallel group double-blinded placebo-controlled trial of daily oral capsules of LDN or placebo for individuals 19-69 years old of both sexes for the treatment of PCFS. 160 participants will be treated with either LDN or placebo for 16 weeks.

Conditions

• Post-Viral Fatigue Syndrome

Interventions

Type	Name	Description
DRUG	Low-Dose Naltrexone	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)
OTHER	Placebo	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)

Timeline

• Start date: 2024-01-15
• Primary completion: 2026-02-15
• Completion: 2026-02-28
• First posted: 2022-06-24
• Last updated: 2026-03-20

Locations

1 site across 1 country: Canada