Disulfiram in Rheumatoid Arthritis

NCT07534332 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 19088
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation and systemic immune activation. Obesity is common among individuals with RA and is associated with increased disease activity, reduced treatment response, and worse functional outcomes. Inflammation in adipose tissue, driven in part by activation of the NLRP3 inflammasome and downstream gasdermin D (GSDMD)-mediated pathways, may contribute to systemic inflammation and RA disease severity. Disulfiram (DSF), an FDA-approved medication for alcohol use disorder, has recently been identified as an inhibitor of GSDMD-mediated inflammatory signaling and pyroptosis. Preclinical studies suggest that DSF reduces inflammasome activation, inflammatory cytokine release, and metabolic dysfunction. This study is a 12-week, randomized, double-blind, placebo-controlled pilot trial designed to evaluate the safety, tolerability, and preliminary efficacy of DSF in overweight and obese adults with active RA despite stable disease-modifying antirheumatic drug (DMARD) therapy. Participants will be randomized to receive either DSF (250 mg daily) or placebo. The primary objective is to assess safety and tolerability. Secondary and exploratory objectives include evaluating the effects of DSF on systemic inflammation, RA disease activity, metabolic parameters, and adipose tissue inflammasome activation. Findings from this study will inform the feasibility and design of larger clinical trials targeting GSDMD-mediated inflammation in RA.

Conditions

Rheumatoid Arthritis; Inflammation; Obesity

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of Disulfiram

  Safety and tolerability will be assessed by the frequency, severity, and relatedness of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0), as well as laboratory abnormalities, vital signs, and patient-reported outcomes.

  Baseline through Week 12

Secondary Outcomes (7)

• Change in Rheumatoid Arthritis Disease Activity (CDAI)

  Baseline and Week 12

• Change in Rheumatoid Arthritis Disease Activity (DAS28-CRP)

  Baseline and Week 12

• Change in Insulin Resistance (HOMA-IR)

  Baseline and Week 12

• Change in Body Composition

  Baseline and Week 12

• Change in Adipose Tissue Inflammasome Activation

  Baseline and Week 12

Study Arms (2)

Disulfiram

EXPERIMENTAL

Participants will receive disulfiram 250 mg orally once daily for 12 weeks in addition to stable background disease-modifying antirheumatic drug (DMARD) therapy.

Drug: Disulfiram (DSF)

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo orally once daily for 12 weeks in addition to stable background disease-modifying antirheumatic drug (DMARD) therapy.

Drug: Placebo

Interventions

Placebo DRUG

Matching placebo will be administered orally once daily for 12 weeks. The placebo will be identical in appearance, packaging, and labeling to disulfiram to maintain blinding.

Placebo

Disulfiram (DSF) DRUG

Disulfiram will be administered orally at a dose of 250 mg once daily for 12 weeks.

Disulfiram

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years Body mass index (BMI) ≥25 kg/m² Diagnosis of rheumatoid arthritis (RA) according to ACR/EULAR classification criteria Active disease defined as Clinical Disease Activity Index (CDAI) \>10 Stable disease-modifying antirheumatic drug (DMARD) therapy for ≥3 months prior to enrollment Willingness to abstain from alcohol for the duration of the study Ability and willingness to comply with study procedures

You may not qualify if:

• Significant liver dysfunction (ALT or AST \>2.5× upper limit of normal) Current or recent alcohol dependence (based on screening, e.g., AUDIT) Known hypersensitivity to disulfiram or other thiuram derivatives Pregnancy or breastfeeding Severe cardiovascular disease (e.g., myocardial infarction, arrhythmia, coronary occlusion) Severe psychiatric illness (e.g., psychosis, suicidal ideation) Neurologic disorders (e.g., epilepsy, peripheral neuropathy, cerebral damage) Chronic or acute renal disease (e.g., nephritis) Hepatic cirrhosis or hepatic insufficiency Use of contraindicated medications (e.g., metronidazole, phenytoin, paraldehyde, alcohol-containing preparations, warfarin) Other autoimmune diseases or active/chronic infections Diabetes mellitus or hypothyroidism Allergy to topical iodine Any condition that, in the opinion of the investigator, would pose undue risk or interfere with study participation

Sponsors & Collaborators

• University of Oklahoma: lead
• Presbyterian Health Foundation: collaborator

Study Sites (1)

University of Oklahoma Health Campus

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Inflammation; Obesity

Interventions

Disulfiram

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Study Officials

• Beatriz Y Hanaoka, MD, MSc

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Beatriz Y Hanaoka, MD, MSc

CONTACT

405-271-3480; beatriz-hanaoka@ou.edu

Natalie Feland, MPH, BSN, RN

CONTACT

405-271-3480; osctr@ou.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study. Participants, investigators, study staff, and outcome assessors will be blinded to treatment assignment. Disulfiram and placebo will be identical in appearance, packaging, and labeling. Randomization codes will be maintained by the investigational pharmacy and will not be accessible to the study team except in the case of a medical emergency requiring unblinding.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized in a 1:1 ratio to receive either disulfiram (250 mg daily) or matching placebo for 12 weeks. Randomization will be stratified by body mass index (BMI) to ensure balanced allocation between groups. Both participants and investigators will be blinded to treatment assignment.

Study Record Dates

• First Submitted: April 9, 2026
• First Posted: April 16, 2026
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)