Low Dose Naltrexone for Chronic Pain From Arthritis (LDN-VA)
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|ClinicalTrials.gov Identifier: NCT03008590|
Recruitment Status : Recruiting
First Posted : January 2, 2017
Last Update Posted : October 22, 2018
|Condition or disease||Intervention/treatment||Phase|
|Osteoarthritis Arthritis, Rheumatoid Arthritis, Psoriatic||Drug: Naltrexone Drug: Placebo||Phase 2|
Chronic pain affects over 100 million Americans, and arthritis is the most common cause. Existing treatments for chronic arthritic pain are only mildly effective, and risks of medications used to treat pain are numerous and continue to be discovered. Treatment of chronic is a high priority research area for VA CSR&D.
Naltrexone is an opioid antagonist that is FDA approved in an oral daily dose of 50 mg to prevent recidivism in alcoholics. At much lower doses of 4 - 4.5 mg daily, however, it has been shown in small, blinded, randomized trials to improve pain in fibromyalgia, gastrointestinal symptoms in Crohn's disease, and quality of life in multiple sclerosis. The only other published data are case reports in complex regional pain syndrome, low back pain, and scleroderma. However, advocacy of low-dose naltrexone (LDN) by internet-based MDs and patients is high, and since LDN can be prescribed off-label, its use greatly exceeds what is justified by evidence. The drug can be prescribed only via compounding pharmacies, so its use costs a patient ~$40/month.
Among the many unproven treatments that are widely used, LDN is of particular interest because results of surveys of patients are particularly impressive, because it is quite safe, and because its benefit is plausible pharmacologically. There is evidence both for modulation of central pain-processing pathways and for down-regulation of inflammatory pathways in microglia. Considering the diversity of conditions proposed to benefit from LDN and the unequivocal need for better approaches to pain relief in chronic conditions, high-quality clinical trials are needed in both inflammatory and non-inflammatory conditions. This small but placebo-controlled study, powered to detect an effect size as small as that seen with NSAIDs or the most beneficial non-pharmacologic approaches, is proposed as a prerequisite for considering a pivotal trial through the VA Cooperative Studies Program.
The proposed study is a randomized, double-blinded, cross-over, placebo-controlled trial in adults with osteoarthritis or inflammatory arthritis and persistent pain. Sixty patients will be enrolled for 16 weeks, during which they will receive LDN for 8 weeks and placebo for 8 weeks. Widely accepted patient-reported outcome measures will be used. The co-primary endpoints are reduction in pain severity or pain's interference with function during 8 weeks of LDN compared to 8 weeks placebo, using the Brief Pain Inventory. Other patient-reported data will be used both as secondary outcomes and as covariates in analyzing determinants of response to treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Low Dose Naltrexone for Chronic Pain in Osteoarthritis and Inflammatory Arthritis|
|Actual Study Start Date :||May 1, 2018|
|Estimated Primary Completion Date :||September 30, 2019|
|Estimated Study Completion Date :||September 30, 2019|
Naltrexone first then placebo
Naltrexone for 8 weeks, then placebo for 8 weeks, blinded cross-over design
One 4.5 mg capsule each evening
One capsule each evening
Placebo first then naltrexone
Placebo for 8 weeks, then naltrexone for 8 weeks, blinded cross-over design
One 4.5 mg capsule each evening
One capsule each evening
- Brief Pain Inventory - Pain Interference [ Time Frame: 16 weeks ]Average of 7 questions on how much pain has interfered with general function, walking ability, mood, normal work, relations with other people, sleep, and enjoyment of life
- Brief Pain Inventory - Pain Severity [ Time Frame: 16 weeks ]Average severity of pain in the past 7 days (0-10)
- painDETECT [ Time Frame: 16 weeks ]Measure of neuropathic pain (0-38)
- Brief Fatigue Inventory [ Time Frame: 16 weeks ]Questionnaire, severity of fatigue and fatigue's interference with activity (0-10 scales).
- PROMIS-29 [ Time Frame: 16 weeks ]Questionnaire, survey of health-related quality of life across 8 domains.
- Beck Depression Inventory-II [ Time Frame: 16 weeks ]Questionnaire measuring severity of depression. Used primarily during screening to exclude enrollment of patients with severe depression, but also as a safety outcome measure during the study.
- Clinical Global Impression of Severity (CGI-S) [ Time Frame: 16 weeks ]7-point scale of patients' self-reporting of severity during the study.
- C reactive protein [ Time Frame: 16 weeks ]Biomarker of inflammation
- DAS-28 [ Time Frame: 16 weeks ]Assessment of disease activity in rheumatoid arthritis (only for patients with rheumatoid arthritis)
- BASDAI [ Time Frame: 16 weeks ]Assessment of disease activity by MD in spondyloarthritis (to be used only for patients with spondyloarthritis)
- Clinical Global Impression of Improvement (CGI-I) [ Time Frame: 16 weeks ]7-point scale of patients' self-reporting of improvement or worsening during the study
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): NCT03008590
|Contact: Paul A Monach, MD PhD||(857) 364-6662||Paul.Monach@va.gov|
|Contact: Maureen Dubreuil, MD||(857) email@example.com|
|United States, Massachusetts|
|VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA||Recruiting|
|Boston, Massachusetts, United States, 02130|
|Contact: Paul A Monach, MD PhD 857-364-6662 Paul.Monach@va.gov|
|Principal Investigator: Paul A. Monach, MD PhD|
|Principal Investigator:||Paul A. Monach, MD PhD||VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA|