Immune Effects of Low-dose Naltrexone in ME/CFS

• ClinicalTrials.gov Identifier: NCT02965768
• Recruitment Status: Suspended
• First Posted: November 17, 2016
• Last Update Posted: October 14, 2020
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Jarred Younger, University of Alabama at Birmingham

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Fatigue Syndrome, Chronic	Drug: Naltrexone HCl	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind trial. An encrypted and password-protected database will contain (1) information about individual group assignment, and (2) blister pack codes (medication will be dispensed in blister packs by investigators based on these codes). An investigator not involved with data collection or participant interactions will randomly assign individuals to the treatment group and provide blister pack ID codes for each individual.
• Primary Purpose: Other
• Official Title: The Immune Effects of Low-dose Naltrexone in People With Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS)
• Study Start Date: January 2016
• Estimated Primary Completion Date: August 1, 2021
• Estimated Study Completion Date: August 1, 2021

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Durability of reduction in plasma inflammatory biomarkers [ Time Frame: Baseline; 12 weeks drug; 24 weeks drug ]
   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.
2. Reduction in self-reported fatigue [ Time Frame: 12 weeks drug ]
   Fatigue will be reported daily on a hand-held computer device.
3. Increase in physical function [ Time Frame: 12 weeks drug ]
   Physical function will be reported weekly on a Patient-Specific Functional Scale.
4. Reduction in self-reported symptoms of (i) depression, (ii) anxiety [ Time Frame: 12 weeks drug ]
   Symptoms of depression and anxiety will be reported weekly on a Hospital Anxiety and Depression Scale.

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

• Principal Investigator: Jarred Younger, PhD; University of Alabama at Birmingham

More Information

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. Review.

• Responsible Party: Jarred Younger, Associate Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02965768
• Other Study ID Numbers: F160525003
• First Posted: November 17, 2016
• Last Update Posted: October 14, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Fatigue Syndrome, Chronic; Syndrome; Fatigue; Disease; Pathologic Processes; Virus Diseases; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Naltrexone; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents