Trial registration: Low-dose Naltrexone for Post-COVID Fatigue Syndrome, Luis Nacul, British Columbia Women's Hospital & Health Centre

Clinical trial registration.

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.

https://clinicaltrials.gov/ct2/show/NCT05430152

 

Personally, when I tried LDN, I found the syrupy liquid mixture, that’s measured out with an oral syringe, more effective than the capsules. It was supplied by Dickson Chemist, Glasgow. I don’t know why, but that was my experience. With the capsules, from a different pharmacy, that I tried before, I only got a hint they were working. I think the liquid mixture may be absorbed better, and faster, and this could have implications for efficacy. LDN is very dose-sensitive, and, this is just speculation, but what if the pharmacokinetics matters? I don’t think anyone knows exactly how LDN works, but one theory is that the temporary blocking of opioid receptors is integral to it, so fast and full absorption of the LDN could matter, to get the best block and unblock effect.

 

Post copied from the Long Covid in the media thread

Long article about treating long covid with LDN in Rolling Stone: Can an Addiction Drug Treat Long Covid?

Digging into the research, Korbutov learned that while naltrexone only has approval from the U.S. Food and Drug Administration (FDA) for treating people recovering from addiction to heroin, morphine, oxycodone, and alcohol, some doctors prescribe it off-label in much smaller doses for chronic conditions like fibromyalgia, multiple sclerosis, and Crohn’s disease.

“Once I looked into the science, I was kind of shocked that it wasn’t more mainstream medication,” Korbutov tells Rolling Stone. “It’s one of those things you have to discover yourself.”

This is, in part, because unlike new-to-the-market blockbuster drugs, pharmaceutical companies don’t stand to profit much from one that’s been around for decades, and, as a result, aren’t spending money promoting it. LDN also has yet to go fully mainstream because the medical establishment has long ignored and dismissed the chronic and invisible conditions it has been used to treat — myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in particular.

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For now, Luis Nacul, MD, PhD, an associate professor at the University of British Columbia’s Faculty of Medicine and the principal investigator of a clinical trial investigating the use of LDN as a potential treatment for post-Covid fatigue, discourages LDN’s off-label use.

“Until this research is completed, we do not recommend the use of LDN for people with Long Covid-19 because it is essential to create the evidence before recommending its use,” Nacul told Rolling Stone in an email. ​