Back to resultsImmune Effects of Low-dose Naltrexone in ME/CFS
Primary Purpose
Fatigue Syndrome, Chronic
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Naltrexone HCl
Sponsored by
About this trial
This is an interventional other trial for Fatigue Syndrome, Chronic
Eligibility 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:
- 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).
Sites / Locations
- University of Alabama at Birmingham
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Other
Arm Label
LDN arm
Placebo/LDN arm
Arm Description
Naltrexone HCl 4.5mg (standard-dose) or 3.0mg (optional-dose) x24 weeks
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.
Outcomes
Primary Outcome Measures
Reduction in plasma inflammatory biomarkers
Levels of plasma IL-1B, TNFa, IL6, IL12, and IL17 will be tested as the primary biomarkers of interest.
Secondary Outcome Measures
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.
Reduction in self-reported fatigue
Fatigue will be reported daily on a hand-held computer device.
Increase in physical function
Physical function will be reported weekly on a Patient-Specific Functional Scale.
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.
Full Information
NCT ID
NCT02965768
First Posted
November 14, 2016
Last Updated
August 30, 2022
Sponsor
University of Alabama at Birmingham
1. Study Identification
Unique Protocol Identification Number
NCT02965768
Brief Title
Immune Effects of Low-dose Naltrexone in ME/CFS
Official Title
The Immune Effects of Low-dose Naltrexone in People With Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Study was temporarily suspended to focus on other projects, but was never resumed. No participants were determined eligible and none started the protocol.
Study Start Date
January 2016 (undefined)
Primary Completion Date
August 25, 2022 (Actual)
Study Completion Date
August 25, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fatigue Syndrome, Chronic
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LDN arm
Arm Type
Active Comparator
Arm Description
Naltrexone HCl 4.5mg (standard-dose) or 3.0mg (optional-dose) x24 weeks
Arm Title
Placebo/LDN arm
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Naltrexone HCl
Other Intervention Name(s)
Low-dose Naltrexone, LDN
Intervention Description
4.5 mg Naltrexone HCl, p.o., nocte (standard-dose); 3.0 mg Naltrexone HCl, p.o., nocte (optional-dose);
Primary Outcome Measure Information:
Title
Reduction in plasma inflammatory biomarkers
Description
Levels of plasma IL-1B, TNFa, IL6, IL12, and IL17 will be tested as the primary biomarkers of interest.
Time Frame
Four-week baseline; 12 weeks drug
Secondary Outcome Measure Information:
Title
Durability of reduction in plasma inflammatory biomarkers
Description
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.
Time Frame
Baseline; 12 weeks drug; 24 weeks drug
Title
Reduction in self-reported fatigue
Description
Fatigue will be reported daily on a hand-held computer device.
Time Frame
12 weeks drug
Title
Increase in physical function
Description
Physical function will be reported weekly on a Patient-Specific Functional Scale.
Time Frame
12 weeks drug
Title
Reduction in self-reported symptoms of (i) depression, (ii) anxiety
Description
Symptoms of depression and anxiety will be reported weekly on a Hospital Anxiety and Depression Scale.
Time Frame
12 weeks drug
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jarred Younger, PhD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24526250
Citation
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.
Results Reference
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Immune Effects of Low-dose Naltrexone in ME/CFS
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