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Not yet recruitingPhase 2

Disulfiram in Rheumatoid Arthritis

Therapeutic Targeting of Gasdermin D-Mediated Pyroptosis to Attenuate Joint Inflammation in Rheumatoid Arthritis

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 75 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: X-rays, Questionnaires, Biopsies

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Metabolic parameters will include fasting glucose, insulin, and insulin resistance (HOMA-IR), as well as body composition assessed by dual-energy X-ray absorptiometry (DEXA) and bioelectrical impedance analysis (BIA)."
  • "RA disease activity will be evaluated using validated measures including CDAI and DAS28-CRP, along with functional assessments such as the Modified Health Assessment Questionnaire (MDHAQ)."
  • "Adipose tissue biopsies will be obtained at baseline and Week 12 to assess inflammasome activation and GSDMD-mediated pathways."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This 12-week study tests the safety and possible benefits of disulfiram, a medicine used to treat alcohol use disorder. It is for overweight or obese adults with active rheumatoid arthritis (RA), a disease where the immune system attacks the joints, despite steady treatment. Participants will get either disulfiram (250 mg daily) or a placebo, a pill with no active medicine.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 18 to 75 years old.
  • Have a body mass index (BMI) of 25 or higher. BMI is a measure of weight compared with height.
  • Have RA that meets standard medical guidelines for diagnosis.
  • Have active RA, with a Clinical Disease Activity Index (CDAI) score above 10.
  • Have been on steady treatment with RA disease-modifying medicines (DMARDs) for at least 3 months.
  • Be willing to avoid alcohol throughout the study.
  • Be able and willing to follow study procedures.

Who can't join

  • Have serious liver problems, including liver blood tests (ALT or AST) above 2.5 times the normal limit, liver scarring, or poor liver function; or have short-term or long-term kidney disease.
  • Have current or recent alcohol dependence, or an allergy to disulfiram, related chemicals called thiurams, or iodine applied to the skin.
  • Be pregnant or breastfeeding.
  • Have severe heart or blood vessel disease, such as a heart attack, abnormal heartbeat, or a blocked heart artery.
  • Have severe mental illness, such as losing touch with reality or thoughts of suicide; or a brain or nerve disorder, such as epilepsy, nerve damage, or brain damage.
  • Take medicines that cannot be used with disulfiram, such as metronidazole, phenytoin, paraldehyde, products containing alcohol, or warfarin.
  • Have another disease where the immune system attacks the body, an active or long-term infection, diabetes, or an underactive thyroid.
  • Have any other condition that the study doctor believes would make participation too risky or interfere with the study.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: 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 \- Exclusion Criteria: 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

Study sites (1)

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