Low-Dose Naltrexone for Post-COVID Fatigue Syndrome

Recruiting at 1 trial location

Overseen By Erin Cooke, BSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Luis Nacul

Must not be taking: Opioids, Naltrexone

Disqualifiers: Pregnancy, Substance misuse, ME/CFS, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests low-dose naltrexone (LDN) to see if it can reduce fatigue and inflammation in people aged 19-69 who have persistent symptoms after recovering from COVID-19. LDN is a small dose of a medication usually used for addiction, which might help by calming the immune system.

Do I have to stop taking my current medications for the trial?

You can continue taking your current medications at the same doses during the trial, unless you need a new medication or dose change as prescribed by a doctor. However, you must stop taking any opioid medications at least 15 days before joining the trial.

What data supports the effectiveness of the drug Low-Dose Naltrexone for treating post-COVID fatigue syndrome?

Low-Dose Naltrexone (LDN) has shown promise in reducing symptoms like fatigue and improving overall function in people with post-COVID conditions, as seen in a review of 59 patients. Additionally, LDN has been used successfully for similar symptoms in other conditions like fibromyalgia and multiple sclerosis, suggesting it may help with post-COVID fatigue. ^{1 2 3 4 5}

Is low-dose naltrexone safe for humans?

Low-dose naltrexone has been used in small studies for various conditions like Crohn's disease and fibromyalgia, and while some people report benefits, others have experienced unpleasant effects such as loss of energy and stomach issues. These effects were generally tolerable, but more research is needed to fully understand its safety. ^{1 2 4 6 7}

How is the drug low-dose naltrexone unique for treating post-COVID fatigue syndrome?

Low-dose naltrexone is unique because it is used off-label for its anti-inflammatory and immune-modulating effects, which may help reduce symptoms like fatigue and improve overall function in post-COVID fatigue syndrome, a condition with no established treatments. ^{1 2 3 8 9}

Research Team

Luis Nacul, MD, PhD

Principal Investigator

WHRI / University of British Columbia

Eligibility Criteria

This trial is for men and women aged 19-69 who've had COVID-19 at least 3 months ago, meet the criteria for Post-COVID Fatigue Syndrome, and can stay on their current meds. They must not have severe liver or kidney issues, recent naltrexone use, opioid use in the last 15 days, a history of substance misuse, or be pregnant/breastfeeding.

Inclusion Criteria

I had COVID-19 more than 3 months ago, confirmed by a test or doctor.

Agree to use effective contraception for the trial duration, as appropriate, if female

I am between 19 and 69 years old.

Exclusion Criteria

I had ME/CFS or fibromyalgia before getting COVID-19.

I have not taken any opioid medications in the last 15 days.

The participant is not an ideal candidate for the study, in the opinion of the investigator, for any other reason that could impact the participant's safety or the results of the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral capsules of Low-Dose Naltrexone (LDN) or placebo for the treatment of Post-COVID Fatigue Syndrome

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Low-Dose Naltrexone
• Placebo

Trial Overview The study tests if low-dose Naltrexone (1-4.5 mg) helps reduce fatigue and inflammation in those with Post-COVID Fatigue Syndrome compared to a placebo. Participants will either receive LDN or an inactive substance without knowing which one they're getting.

Participant Groups

Group I: Low-Dose Naltrexone Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Luis Nacul

Lead Sponsor

Trials

1

Recruited

160+

Vancouver Island Health Authority

Collaborator

Trials

17

Recruited

4,700+

Fraser Health

Collaborator

Trials

49

Recruited

708,000+

Women's Health Research Institute of British Columbia

Collaborator

Trials

8

Recruited

16,600+

Vancouver Coastal Health

Collaborator

Trials

41

Recruited

717,000+

Providence Health & Services

Collaborator

Trials

131

Recruited

827,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

BC Women's Hospital & Health Centre

Collaborator

Trials

15

Recruited

1,010,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Provincial Health Services Authority

Collaborator

Trials

40

Recruited

31,900+

Findings from Research

Approximately 43% of individuals who have had COVID-19 experience Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), with symptoms including fatigue and sleep disturbances, highlighting a significant public health concern.

In a retrospective study of 59 patients, low-dose naltrexone (LDN) showed promise in reducing symptoms and improving functional status in those with PASC, suggesting it may be a potential therapeutic option that warrants further investigation in controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. Bonilla, H., Tian, L., Marconi, VC., et al.[2023]

Low-dose naltrexone (LDN) has shown potential efficacy in treating chronic immune-modulated disorders, with case reports indicating varied responses in patients with chronic fatigue syndrome, ranging from significant improvement to partial symptom relief.

Despite promising anecdotal evidence and small-scale trials for other conditions, there is a lack of clinical trials specifically investigating LDN for chronic fatigue syndrome, suggesting a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone as a treatment for chronic fatigue syndrome. Bolton, MJ., Chapman, BP., Van Marwijk, H.[2020]

A study involving persons with multiple sclerosis (PwMS) indicated that low-dose naltrexone (LDN) therapy significantly reduced self-reported anxiety and depression during the early months of COVID-19, compared to those on standard disease-modifying therapies (DMTs).

LDN, which is a non-toxic and inexpensive treatment, may offer a beneficial option for managing anxiety in PwMS, particularly during stressful times like a pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic. McLaughlin, PJ., Odom, LB., Arnett, PA., et al.[2022]

Post-COVID syndrome, defined by the WHO, affects individuals with a history of COVID-19 and includes core symptoms like fatigue, dyspnea, and cognitive dysfunction, impacting daily life and occurring in over 30% of patients.

Treatment options for post-COVID fatigue include both pharmacological approaches, such as stimulants and antidepressants, and nonpharmacological strategies like cognitive behavioral therapy and exercise, supported by evidence from meta-analyses on similar fatigue conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Post-COVID syndrome-Focus fatigue]. Hellwig, S., Domschke, K.[2022]

The ReCOVer study is a randomized controlled trial involving 114 participants aimed at testing the efficacy of a 17-week cognitive behavioural therapy (CBT) program called Fit after COVID to reduce severe fatigue in individuals who have recovered from COVID-19.

If successful, this intervention could significantly alleviate one of the most common and distressing long-term symptoms of COVID-19, potentially improving overall health outcomes for patients suffering from post-acute sequelae of SARS-CoV-2 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol. Kuut, TA., Müller, F., Aldenkamp, A., et al.[2022]

A 33-year-old woman developed symptoms of narcolepsy just two weeks after recovering from COVID-19, suggesting a potential link between COVID-19 and the onset of narcolepsy in susceptible individuals.

Clinicians are advised to evaluate patients experiencing post-COVID fatigue and hypersomnia for narcolepsy, as immune activation from the virus may trigger this sleep disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Narcolepsy following COVID-19: A case report and review of potential mechanisms. Roya, Y., Farzaneh, B., Mostafa, AD., et al.[2023]

In a study involving ten opiate-free volunteers, naltrexone was administered over three weeks, leading to three participants dropping out due to unpleasant side effects, while the remaining seven experienced tolerable but still aversive effects.

A separate group of ten subjects receiving single doses of naltrexone also reported significant aversive reactions, including loss of energy, gastrointestinal issues, and mental depression, which may hinder the drug's acceptance as a treatment for opiate dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aversive effects of naltrexone in subjects not dependent on opiates. Hollister, LE., Johnson, K., Boukhabza, D., et al.[2019]

Low dose naltrexone (LDN) may help reduce pain and improve quality of life in patients with fibromyalgia, based on a systematic review of three small studies, but the overall evidence is considered weak due to high risk of bias and small sample sizes.

Some evidence suggests that inflammatory markers, such as erythrocyte sedimentation rate (ESR) and cytokines, may play a role in how LDN works, but more research is needed, especially with larger and more diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic literature review on the clinical efficacy of low dose naltrexone and its effect on putative pathophysiological mechanisms among patients diagnosed with fibromyalgia. Partridge, S., Quadt, L., Bolton, M., et al.[2023]

Low dose naltrexone (LDN) shows potential as an off-label treatment for pain in conditions like fibromyalgia, multiple sclerosis, and Crohn's disease, but the current evidence is limited and not robust.

Due to the lack of sufficient randomized controlled trials demonstrating its efficacy over placebo, LDN cannot be recommended as a first-line therapy for pain management at this time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Low dose naltrexone for treatment of pain]. Plesner, KB., Vægter, HB., Handberg, G.[2017]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone as a treatment for chronic fatigue syndrome. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

[Post-COVID syndrome-Focus fatigue]. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Narcolepsy following COVID-19: A case report and review of potential mechanisms. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Aversive effects of naltrexone in subjects not dependent on opiates. [2019]

8. England pubmed.ncbi.nlm.nih.gov

A systematic literature review on the clinical efficacy of low dose naltrexone and its effect on putative pathophysiological mechanisms among patients diagnosed with fibromyalgia. [2023]

9. Denmark pubmed.ncbi.nlm.nih.gov

[Low dose naltrexone for treatment of pain]. [2017]