Low-dose Naltrexone for Post-COVID Fatigue Syndrome
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| ClinicalTrials.gov Identifier: NCT05430152 |
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Recruitment Status :
Recruiting
First Posted : June 24, 2022
Last Update Posted : March 1, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Post-Viral Fatigue Syndrome | Drug: Low-Dose Naltrexone Other: Placebo | Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Randomized parallel group double-blinded placebo-controlled trial |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Double-blinded placebo-controlled |
| Primary Purpose: | Treatment |
| Official Title: | A Double Blind Randomized Trial of Low-dose Naltrexone for Post-COVID Fatigue Syndrome |
| Actual Study Start Date : | January 15, 2024 |
| Estimated Primary Completion Date : | December 2024 |
| Estimated Study Completion Date : | December 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Low-Dose Naltrexone
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.
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Drug: Low-Dose Naltrexone
Study drug dosing schedule (LDN):
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Placebo Comparator: Placebo
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.
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Other: Placebo
Study drug dosing schedule (Placebo; capsules made to match LDN doses):
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- Fatigue Intensity [ Time Frame: 16 weeks ]Change in the Fatigue Severity Scale (FSS) total score by 4.7 points or over
- Pain Severity [ Time Frame: 16 weeks ]Change in Pain Visual Analogue Scale (VAS) 0-10 score
- Symptom Severity [ Time Frame: 16 weeks ]Change in Patient Phenotyping Questionnaire Short Form (PQSymp-12) score
- Activity Levels [ Time Frame: 16 weeks ]Changes in average number of steps over 7 days
- Self-reported Quality of Life [ Time Frame: 16 weeks ]Change in EuroQol-5 Dimension 5-level (EQ-5D-5L) total score
- Exploratory outcome: Changes in inflammatory marker values in peripheral blood [ Time Frame: 16 weeks ]Changes in Interleukin 6 (IL-6), Interferon gamma (IFNγ), C-reactive protein (hsCRP), & cytokine profile (Human High Sensitivity T-Cell 14-plex Discovery Assay® Array) values
- Exploratory outcome: Disease Severity [ Time Frame: 16 weeks ]Change in Creatine kinase (CK) plasma concentration
- Exploratory outcome: Reverse triiodothyronine (rT3) profile (as an indirect marker of disease severity) [ Time Frame: 16 weeks ]Change in concentration of Reverse triiodothyronine (rT3) (in conjunction Thyroid stimulating hormone (TSH), Free Triiodothyronine (free T3) & Free Thyroxine (free T4))
- Exploratory outcome: Visual Analogue Scale (VAS) Fatigue Score [ Time Frame: 16 weeks ]Change in the fatigue Visual Analogue Scale (VAS) 0-10 score
- Exploratory outcome: Prevalence markers of Postural Orthostatic Tachycardia Syndrome (POTS) or Postural Hypotension [ Time Frame: 16 weeks ]Change in the prevalence of POTS or postural hypotension symptoms based on serial blood pressure and heart rate measurement
- Exploratory outcome: Sleep [ Time Frame: 16 weeks ]Changes in the Sleep Questionnaire (SQ-2)
- Exploratory outcome: Sleep [ Time Frame: 16 weeks ]Changes in the self-reported sleep Visual Analogue Scale (VAS)
- Exploratory outcome: Depression [ Time Frame: 16 weeks ]Changes in the Patient Health Questionnaire (PHQ-9) Score
- Exploratory outcome: Anxiety [ Time Frame: 16 weeks ]Changes in the Generalized Anxiety Disorder (GAD-7) Score
- Exploratory outcome: Self-reported Health [ Time Frame: 16 weeks ]Changes in the self-reported Visual Analogue Scale (VAS) health scale (EQ-5D-5L)
- Exploratory outcome: Improves low AM blood cortisol [ Time Frame: 16 weeks ]Changes in concentration of AM blood cortisol values
- Exploratory outcome: Improves Adrenocorticotropic hormone (ACTH) [ Time Frame: 16 weeks ]Changes in concentration of ACTH hormone values
- Exploratory outcome: Improves Functional Status [ Time Frame: 16 weeks ]Changes in Post-COVID-19 Functional Status Scale
- Clinical Endurance/ Strength Parameters [ Time Frame: 16 weeks ]Changes in maximum hand grip strength over 3 attempts
- Clinical Endurance/ Strength Parameters [ Time Frame: 16 weeks ]Changes in sit and stand test in 30 seconds
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 19 Years to 69 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- Pregnant, planning to become pregnant, or breastfeeding
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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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05430152
| Contact: Travis Boulter | 236-990-9519 | LDNtrial@phsa.ca | |
| Contact: Erin Cooke, BSc | 236-990-9519 | LDNtrial@phsa.ca |
| Canada, British Columbia | |
| BC Women's Hospital + Health Centre | Recruiting |
| Vancouver, British Columbia, Canada, V6H 3N1 | |
| Contact: Travis Boulter 236-990-9519 LDNtrial@phsa.ca | |
| Principal Investigator: | Luis Nacul, MD, PhD | BC Women's Hospital + Health Centre/ University of British Columbia |
| Responsible Party: | Luis Nacul, Research Director, Complex Chronic Diseases Program, BC Women's Hospital + Health Centre/ Clinical Associate Professor, University of British Columbia, University of British Columbia |
| ClinicalTrials.gov Identifier: | NCT05430152 |
| Other Study ID Numbers: |
H21-02254 |
| First Posted: | June 24, 2022 Key Record Dates |
| Last Update Posted: | March 1, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | At the time of publication, the study data may be deposited on a publicly accessible location. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Post-COVID Fatigue Syndrome Long-COVID COVID-19 SARS-CoV-2 |
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Fatigue Syndrome, Chronic Syndrome Fatigue Disease Pathologic Processes Muscular Diseases Musculoskeletal Diseases Encephalomyelitis Neuroinflammatory Diseases Nervous System Diseases |
Neuromuscular Diseases Chronic Disease Disease Attributes Naltrexone Alcohol Deterrents Narcotic Antagonists Physiological Effects of Drugs Sensory System Agents Peripheral Nervous System Agents |