Low Dose Naltrexone for Chronic Pain From Arthritis

NCT03008590 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NURB-008-16S
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Over 100 million Americans report chronic pain. Veterans are disproportionately affected for multiple reasons, including injuries and post-traumatic stress disorder. Treatment for chronic pain is a priority research area for the VA. One of the most common causes of chronic pain is osteoarthritis (OA). OA is attributable to "wear and tear," but reasons for pain are complex. Inflammatory arthritis (IA) includes multiple severe diseases that affect 2-3% of persons and require treatment with immune-suppressive drugs to prevent joint destruction. Pain often persists despite effective treatment. Pain in arthritis results from multiple sources: inflammation, perception of pain in the joint, and interpretation of pain by the brain. Unfortunately, management of pain in arthritis remains a challenge. Low dose naltrexone is a widely used but unproven "alternative" approach to chronic pain. It is attractive for study because it is safe and is proposed to work on all three pathways that contribute to pain. A small but high-quality clinical trial is needed to determine whether to invest in definitive studies.

Conditions

Osteoarthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic

Keywords

Pain management; Naltrexone; Controlled clinical trials, randomized

Outcome Measures

Primary Outcomes (1)

• Brief Pain Inventory - Pain Interference

  Sum of 7 questions (each on a 0-10 scale, therefore 0-70 total) on how much pain has interfered with general function, walking ability, mood, normal work, relations with other people, sleep, and enjoyment of life. Higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks of naltrexone, or after 8 weeks of placebo.

  8 and 16 weeks, ie after 8 weeks naltrexone or 8 weeks placebo

Secondary Outcomes (10)

• Brief Pain Inventory - Pain Severity

  8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

• painDETECT

  8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

• Brief Fatigue Inventory

  8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

• Beck Depression Inventory-II

  8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

• Clinical Global Impression of Severity (CGI-S)

  8 and16 weeks, ie after 8 weeks naltrexone and 8 weeks placebo

Study Arms (2)

Naltrexone first then placebo

OTHER

Naltrexone for 8 weeks, then placebo for 8 weeks, blinded cross-over design

Drug: Naltrexone; Drug: Placebo

Placebo first then naltrexone

OTHER

Placebo for 8 weeks, then naltrexone for 8 weeks, blinded cross-over design

Drug: Naltrexone; Drug: Placebo

Interventions

Naltrexone DRUG

One 4.5 mg capsule each evening

Naltrexone first then placebo; Placebo first then naltrexone

Placebo DRUG

One capsule each evening

Naltrexone first then placebo; Placebo first then naltrexone

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria in order to be eligible for enrollment:
• Veteran or otherwise eligible for VA benefits, able to travel to VA Boston
• One or more of the following chronic conditions:
• osteoarthritis
• rheumatoid arthritis
• non-axial spondyloarthritis
• Average daily pain interference with function (average of the 7 parts of question 9 on the Brief Pain Inventory) rated at least 4 on a scale of 0-10, and no higher than 9
• No change in medication in the past 8 weeks made with the expectation of improving pain
• No plan to start another medication or a non-pharmacologic treatment regimen likely to affect pain during the next 16 weeks
• Age at least 18
• Registered for medical care in the VA Boston Healthcare System
• Capable of informed consent, and willingness to comply with study procedures, including receipt of weekly phone calls from the study coordinator

You may not qualify if:

• Current use of opioids including tramadol
• Pregnant, breast feeding, or unwilling to engage in contraceptive practices if sexually active and capable of conceiving
• Schizophrenia, bipolar disorder, or poorly controlled depression or anxiety
• Previous use of low-dose naltrexone
• Back pain described by the patient as greater in severity than arthritic pain in a non-axial location
• Significant kidney disease, defined as glomerular filtration rate \< 30 ml/min
• Liver cirrhosis. There is no specific screening procedure to exclude cirrhosis.
• Painful peripheral neuropathy. There is no specific screening procedure.
• Plan to have surgery during the next 16 weeks
• Inconsistency in self-reporting at the screening visit. BPI, PainDETECT, WOMAC, and PROMIS-29 all contain 0-10 scales of average pain intensity, although the times listed vary from 1-4 weeks. The severity reported on these three scales cannot differ by more than 1.
• Other qualitative circumstances that the investigator feels would make the patient a poor candidate for this clinical trial, such as an unstable social situation or unreliable transportation

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130, United States

Location

Related Publications (1)

• Beaudette-Zlatanova B, Lew RA, Otis JD, Branch-Elliman W, Bacorro E, Dubreuil M, Eyvazzadeh C, Kaur M, Lazzari AA, Libbey C, Monach PA. Pilot Study of Low-dose Naltrexone for the Treatment of Chronic Pain Due to Arthritis: A Randomized, Double-blind, Placebo-controlled, Crossover Clinical Trial. Clin Ther. 2023 May;45(5):468-477. doi: 10.1016/j.clinthera.2023.03.013. Epub 2023 Apr 10.

  PMID: 37045708 DERIVED

MeSH Terms

Conditions

Osteoarthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Agnosia

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr Paul Monach, Chief, Rheumatology Section
• Organization: VA Boston Healthcare System

Paul.Monach@va.gov

857-364-5552

Study Officials

• Paul A. Monach, MD PhD

  VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: January 2, 2017
• Study Start: May 1, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: March 3, 2021
• Results First Posted: March 3, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: ICF to be posted within 3 months per VA policy. De-identified dataset to be included as supplementary material with publication, anticipated to be within 12 months of study completion.

Locations

US (1)