Immune Effects of Low-dose Naltrexone in ME/CFS

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Fatigue Syndrome, Chronic
• Intervention / Treatment: Drug: Naltrexone HCl

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama At Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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:

1. Blood draw contraindicated or otherwise not able to be performed
2. High-sensitivity c-reactive protein (HS-CRP) ≥3 mg/L
3. Erythrocyte sedimentation rate (ESR) >60 mm/hr
4. Positive rheumatoid factor
5. Positive anti-nuclear antibody (ANA)
6. Levels of thyroid stimulating hormone or free thyroxine outside UAB lab reference values
7. Diagnosed rheumatological or auto-immune condition
8. Clotting disorder
9. Use of blood thinning medication
10. Oral temperature >100˚F at baseline
11. Febrile illness or use of antibiotics in the 4 weeks before study commencement;
12. Planned surgery or procedures during the study period, or operated on in the 4 weeks before study commencement
13. Pregnant or planning on becoming pregnant within 6 months
14. Regular use of any anti-inflammatory medication (such as aspirin, ibuprofen, naproxen)
15. Known allergy or adverse effects following naltrexone or naloxone administration
16. Opioid use (self-reported or positive on urine test)
17. Significant psychological comorbidity that in the discretion of the investigator compromises study integrity and/or a baseline HADS depression subscale score of ≥16
18. Current litigation or worker's compensation claim
19. Current participation in another treatment trial
20. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: LDN arm; Naltrexone HCl 4.5mg (standard-dose) or 3.0mg (optional-dose) x24 weeks	Drug: Naltrexone HCl; 4.5 mg Naltrexone HCl, p.o., nocte (standard-dose); 3.0 mg Naltrexone HCl, p.o., nocte (optional-dose); Other Names: Low-dose Naltrexone; LDN
Other: Placebo/LDN arm; 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; 4.5 mg Naltrexone HCl, p.o., nocte (standard-dose); 3.0 mg Naltrexone HCl, p.o., nocte (optional-dose); Other Names: Low-dose Naltrexone; LDN

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham

Publications and helpful links

General Publications

• Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): August 25, 2022
• Study Completion (Actual): August 25, 2022

Study Registration Dates

• First Submitted: November 14, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Syndrome; Fatigue; Fatigue Syndrome, Chronic; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: F160525003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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