Low-Dose Naltrexone for Post-COVID Fatigue Syndrome
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen ByLuis Nacul, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Luis Nacul
Must not be taking: Opioids, Naltrexone
Disqualifiers: Pregnancy, Substance misuse, ME/CFS, others
Prior Safety Data
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.
12345Is 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.
12467How 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.
12389Eligibility 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.
+3 more
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
+8 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Low-Dose NaltrexoneExperimental Treatment1 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: PlaceboPlacebo Group1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Women's Health Research InstituteVancouver, Canada
BC Women's Hospital + Health CentreVancouver, Canada
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Who Is Running the Clinical Trial?
Luis NaculLead Sponsor
Vancouver Island Health AuthorityCollaborator
Fraser HealthCollaborator
Women's Health Research Institute of British ColumbiaCollaborator
Vancouver Coastal HealthCollaborator
Providence Health & ServicesCollaborator
University of British ColumbiaCollaborator
BC Women's Hospital & Health CentreCollaborator
Canadian Institutes of Health Research (CIHR)Collaborator
Provincial Health Services AuthorityCollaborator
References
Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. [2023]The global prevalence of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) stands at approximately 43 % among individuals who have previously had acute COVID-19. In contrast, in the United States, the National Center for Health Statistics (NCHS) estimates that around 11 % of individuals who have been infected with SARS-CoV-2 go on to experience long COVID. The underlying causes of PASC remains under investigation, and there are no currently established FDA-approved therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increase systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. We performed a retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status. This observation warrants testing in rigorous, randomized, placebo-controlled clinical trials.
Low-dose naltrexone as a treatment for chronic fatigue syndrome. [2020]Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn's disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome. This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances. This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12 mg. Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.
Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic. [2022]Persons with multiple sclerosis (PwMS) have been considered at high risk for vaccination and/or acquisition of COVID-19 related to their reduced immune systems and daily regimen of immune suppressing therapy. Substantiated and unsubstantiated reports on these unknown circumstances increased anxiety and depression. Low-dose naltrexone (LDN) is a potentially effective off-label therapy shown to be effective at controlling fatigue for several autoimmune disorders including MS. This study utilized a small population of PwMS from central Pennsylvania in order to determine whether LDN therapy altered their perceived anxiety or depression during the early months of COVID-19. Utilizing mailed surveys, self-reported anxiety and depression scores were found to be significantly lower for PwMS who were prescribed LDN either alone or as an adjuvant to a standard disease modifying therapy (DMT) in comparison to those on oral disease-modifying therapies (DMTs). The data suggest that the non-toxic, inexpensive biotherapeutic may be beneficial in lessening anxiety.
[Post-COVID syndrome-Focus fatigue]. [2022]The World Health Organization (WHO) defines post-coronavirus disease 2019 (COVID-19) as a condition which occurs in individuals with a history of probable or confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection 3 months after the onset of COVID-19 symptoms, lasts for at least 2 months and cannot be explained by an alternative diagnosis. Core symptoms of post-COVID syndrome are fatigue, dyspnea and cognitive dysfunction, which have an impact on everyday functional level. Neuropsychiatric late sequelae are common in COVID-19 patients, with incidence rates over 30%. Beside the abovementioned core symptoms, sleep disorders, depression and anxiety show increased incidences. According to current opinion, associated neuropsychiatric symptoms are subsumed under the term post-COVID syndrome but are also interpreted as comorbidities, which can promote the manifestation of a post-COVID syndrome. The key symptom fatigue shows symptom overlapping and comorbidity with psychiatric disorders. Imaging studies indicate an organic correlate of fatigue in post-COVID patients. Furthermore, psychosocial aspects and psychiatric comorbidities, such as depression and anxiety disorders as modulating and therefore potentially treatable factors were identified. Treatment of fatigue consists of pharmacological management with stimulants and antidepressants as well as nonpharmacological strategies, most notably cognitive behavioral therapy and exercise-focused interventions. The evidence for this comes from meta-analyses of tumor-associated or post-viral fatigue.
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]Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2.
Narcolepsy following COVID-19: A case report and review of potential mechanisms. [2023]The immune activation in COVID-19 may trigger narcolepsy in vulnerable patients. We suggest clinicians carefully evaluate patients with post-COVID fatigue and hypersomnia for primary sleep disorders, specifically narcolepsy.
Aversive effects of naltrexone in subjects not dependent on opiates. [2019]Naltrexone was given to ten opiate-free volunteer subjects following the same dosage schedule used for initiating treatment of opiate-dependent persons. During the three-week initiation period, three subjects dropped from the study owing to aversive effects of the drug. The remaining seven subjects reported similar unpleasant but tolerable effects. A separate group of ten volunteer subjects was given single doses of 50 or 100 mg of naltrexone or a naltrexone placebo on three separate occasions using blind controls. These subjects also reported aversive effects. The principal symptoms reported were loss of energy, gastrointestinal disturbances and mental depression. It is possible that these aversive reactions of naltrexone have limited acceptance of the drug as a treatment for opiate-dependent persons.
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]Low dose naltrexone (LDN) is used off-label by many individuals with fibromyalgia to help manage their pain. There is no current systematic literature review summarising the evidence to support this use of LDN. The objectives of this study were to evaluate if patients with fibromyalgia prescribed LDN have reduced pain scores and greater quality of life compared with those allocated to placebo in randomized controlled trials. Secondly to determine if changes in inflammatory markers and brain structure and function are observed among patients with fibromyalgia taking LDN.
[Low dose naltrexone for treatment of pain]. [2017]Recent years have seen an increasing interest in the use of low dose naltrexone (LDN) for off-label treatment of pain in diseases as fibromyalgia, multiple sclerosis and morbus Crohn. The evidence is poor, with only few randomized double-blind placebo-controlled studies. The studies currently available are reviewed in this paper. LDN could be a potentially useful drug in the future for the treatment of pain in fibromyalgia, but more studies are needed to verify that it is superior to placebo, and currently it cannot be recommended as first-line therapy.