Immune Effects of Low-dose Naltrexone in ME/CFS

Study Overview
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Brief Summary
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The main objective of this study is to test if naltrexone, when taken in low doses, has an anti-inflammatory effect that may be associated with positive clinical outcomes in people with chronic fatigue syndrome (CFS). In part, the present study, is a continuation of prior work in which we showed that chronic fatigue symptoms are associated with immune activity, and that low-dose naltrexone might exert anti-inflammatory effects in fibromyalgia, which is thought to share some pathophysiological and clinical characteristics with CFS.

Official Title
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The Immune Effects of Low-dose Naltrexone in People With Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS)

Conditions
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Fatigue Syndrome, Chronic

Intervention / Treatment
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* Drug: Naltrexone HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Meet the 1994 Case Definition criteria for CFS (assessed through semi-structured interview and the DePaul University Fatigue Questionnaire): Criteria: Severe chronic fatigue ≥6 consecutive months not due to ongoing exertion or other medical condition associated with fatigue; Fatigue interferes with daily activities and work; Reports ≥4 symptoms that started with or after the fatigue, from: Post-exertion malaise >24 hours Unrefreshing sleep Short-term memory or concentration impairment Muscle pain Joint pain without swelling or redness Headaches of a new type/pattern/severity Lymph node tenderness Frequent or recurring sore throat 3. CFS symptoms for ≥12 months 4. Participant completes daily self-report during the 4-week baseline period; 5. Able to attend UAB on all scheduled appointments Exclusion Criteria: Blood draw contraindicated or otherwise not able to be performed High-sensitivity c-reactive protein (HS-CRP) ≥3 mg/L Erythrocyte sedimentation rate (ESR) >60 mm/hr Positive rheumatoid factor Positive anti-nuclear antibody (ANA) Levels of thyroid stimulating hormone or free thyroxine outside UAB lab reference values Diagnosed rheumatological or auto-immune condition Clotting disorder Use of blood thinning medication Oral temperature >100˚F at baseline Febrile illness or use of antibiotics in the 4 weeks before study commencement; Planned surgery or procedures during the study period, or operated on in the 4 weeks before study commencement Pregnant or planning on becoming pregnant within 6 months Regular use of any anti-inflammatory medication (such as aspirin, ibuprofen, naproxen) Known allergy or adverse effects following naltrexone or naloxone administration Opioid use (self-reported or positive on urine test) Significant psychological comorbidity that in the discretion of the investigator compromises study integrity and/or a baseline HADS depression subscale score of ≥16 Current litigation or worker's compensation claim Current participation in another treatment trial Vaccinated in the 4 weeks before study commencement (vaccination during the study period is allowed as long as the drug is administered at least 4 weeks prior to a study blood draw).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LDN arm<br>Naltrexone HCl 4.5mg (standard-dose) or 3.0mg (optional-dose) x24 weeks | Drug: Naltrexone HCl<br>* 4.5 mg Naltrexone HCl, p.o., nocte (standard-dose); 3.0 mg Naltrexone HCl, p.o., nocte (optional-dose);<br>* Other names: LDN;|
| Other: Placebo/LDN arm<br>Naltrexone HCl 4.5mg (standard-dose) or 3.0mg (optional-dose) Placebo Individuals will be switched between drugs as per approved schedule during the 24 weeks. | Drug: Naltrexone HCl<br>* 4.5 mg Naltrexone HCl, p.o., nocte (standard-dose); 3.0 mg Naltrexone HCl, p.o., nocte (optional-dose);<br>* Other names: LDN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in plasma inflammatory biomarkers | Levels of plasma IL-1B, TNFa, IL6, IL12, and IL17 will be tested as the primary biomarkers of interest. | Four-week baseline; 12 weeks drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durability of reduction in plasma inflammatory biomarkers | Levels of plasma IL-1B, TNFa, IL6, IL12, and IL17 will be tested as the primary biomarkers of interest. 24 weeks vs 12 weeks drug. | Baseline; 12 weeks drug; 24 weeks drug | 
| Reduction in self-reported fatigue | Fatigue will be reported daily on a hand-held computer device. | 12 weeks drug | 
| Increase in physical function | Physical function will be reported weekly on a Patient-Specific Functional Scale. | 12 weeks drug | 
| Reduction in self-reported symptoms of (i) depression, (ii) anxiety | Symptoms of depression and anxiety will be reported weekly on a Hospital Anxiety and Depression Scale. | 12 weeks drug |