Post-Viral Fatigue SyndromePhase 2NCT05430152
Low-dose Naltrexone for Post-COVID Fatigue Syndrome
A Phase 2 study testing Low-Dose Naltrexone in people with Post-Viral Fatigue Syndrome, run by Luis Nacul at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 69 years
- Conditions the study is for
- Post-Viral Fatigue Syndrome
- What is being tested?
- Low-Dose Naltrexone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteCanada
- Study dates
- 15 Jan 2024to 28 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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:
- As regular use of opioid medications is an exclusion criterion, we will do a quality control check with the first 16 participants to test for the presence of opioids in their urine. Any participants with a positive test, will be excluded from the study, and such finding will be discussed at the Trial Steering Committee or DSMB for potential trial modification.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Women's Health Research Institute
Vancouver, British Columbia, V6H 3N1
About this study
Official title: A Double Blind Randomized Trial of Low-dose Naltrexone for Post-COVID Fatigue Syndrome
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.
Read the 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
- Being tested
- Low-Dose Naltrexone, Placebo
- Keywords
- Post-COVID Fatigue Syndrome, Long-COVID, COVID-19, SARS-CoV-2
- Medical subject headings
- Fatigue Syndrome, Chronic, Post-Acute COVID-19 Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-Dose NaltrexoneDrug
Also called LDN
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)
PlaceboOther
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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue Intensity
Change in the Fatigue Severity Scale (FSS) total score by 4.7 points or over
Measured: 16 weeks
Secondary outcomes (4)
Pain Severity
Change in Pain Visual Analogue Scale (VAS) 0-10 score
Measured: 16 weeks
Symptom Severity
Change in Patient Phenotyping Questionnaire Short Form (PQSymp-12) score
Measured: 16 weeks
Activity Levels
Changes in average number of steps over 7 days
Measured: 16 weeks
Self-reported Quality of Life
Change in EuroQol-5 Dimension 5-level (EQ-5D-5L) total score
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2022
- Study start15 Jan 2024
- Primary completion15 Feb 2026
- Study completion28 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-Viral Fatigue SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized parallel group double-blinded placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Luis Nacul
- Sponsor type
- University, hospital or other
- Collaborators
- University of British Columbia, Canadian Institutes of Health Research (CIHR), Provincial Health Services Authority British Columbia, Women's Health Research Institute of British Columbia
- Responsible party
- Sponsor-investigator, Luis Nacul, University of British Columbia
- Investigators
- Luis Nacul, MD, PhD, Principal investigator, WHRI / University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05430152
- Sponsor's protocol ID
- H21-02254
- Status last verified
- Mar 2026
- First submitted
- 10 Jun 2022
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: At the time of publication, the study data may be deposited on a publicly accessible location.
Publications
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.
PubMed 38740499
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Randomized Trial of Low-dose Naltrexone for Post-COVID Fatigue Syndrome
- ClinicalTrials.gov ID
- NCT05430152
- Acronym / sponsor ID
- H21-02254
- Conditions
- Post-Viral Fatigue Syndrome
- Keywords
- Post-COVID Fatigue Syndrome, Long-COVID, COVID-19, SARS-CoV-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Luis NaculUniversity, hospital or other
- Collaborators
- University of British Columbia, Canadian Institutes of Health Research (CIHR), Provincial Health Services Authority British Columbia, Women's Health Research Institute of British Columbia
- Study start
- 15 Jan 2024 (actual)
- Primary completion
- 15 Feb 2026 (actual)
- Study completion
- 28 Feb 2026 (actual)
- First posted
- 24 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized parallel group double-blinded placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Low-Dose Naltrexone | Experimental | Drug: Low-Dose NaltrexoneThe 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. |
| Placebo | Placebo comparator | Other: PlaceboMatching 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. |
Who may qualify
- Ages
- 19 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (16 listed)
- Pregnant, planning to become pregnant, or breastfeeding
- Opioid medications:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-Dose NaltrexoneAlso: LDNStudy 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) | Drug | Low-Dose Naltrexone |
| PlaceboStudy 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) | Other | Placebo |
Primary outcome
Fatigue Intensity
Time frame: 16 weeks
Change in the Fatigue Severity Scale (FSS) total score by 4.7 points or over
4 secondary outcomes
Pain Severity
Time frame: 16 weeks
Symptom Severity
Time frame: 16 weeks
Activity Levels
Time frame: 16 weeks
Self-reported Quality of Life
Time frame: 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Derived from this study: PubMed 38740499Naik 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.
- Individual participant dataSharing planned: Yes. At the time of publication, the study data may be deposited on a publicly accessible location.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis Nacul, MD, PhD principal investigator
WHRI / University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low-Dose Naltrexone in people with Post-Viral Fatigue Syndrome, run by Luis Nacul at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue Intensity (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05430152, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2026.