[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07534332":3,"trial-entities:NCT07534332":107,"trial-summary:NCT07534332":110},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":22,"study_type":23,"primary_purpose":24,"phases":25,"enrollment_info":27,"interventions":30,"primary_outcomes":41,"secondary_outcomes":46,"sex":69,"minimum_age":70,"maximum_age":71,"healthy_volunteers":15,"eligibility_criteria":72,"std_ages":76,"locations":79,"central_contacts":98,"overall_officials":103,"references":105,"see_also_links":106},"NCT07534332","19088P","Disulfiram in Rheumatoid Arthritis","Therapeutic Targeting of Gasdermin D-Mediated Pyroptosis to Attenuate Joint Inflammation in Rheumatoid Arthritis","NOT_YET_RECRUITING","2028-04-30","2026-07","2026-07-27","2026-09","University of Oklahoma","OTHER",false,"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.\n\nDisulfiram (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.\n\nThis 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.\n\nThe 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.","Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and systemic immune activation. Obesity is highly prevalent among individuals with RA and is associated with increased disease activity, reduced response to therapy, and greater functional impairment. Emerging evidence suggests that adipose tissue inflammation plays a key role in amplifying systemic immune activation in RA. In obesity, macrophage infiltration of adipose tissue leads to activation of the NLRP3 inflammasome, resulting in the production of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-18. These processes contribute to systemic inflammation and may exacerbate RA disease activity.\n\nGasdermin D (GSDMD) is a critical downstream effector of inflammasome activation. Cleavage of GSDMD by caspase-1 results in pore formation in the cell membrane, enabling the release of inflammatory cytokines and inducing pyroptosis, a lytic form of programmed cell death. While therapies targeting IL-1β have demonstrated limited efficacy in RA, inhibition of GSDMD represents a broader strategy to suppress multiple inflammasome-mediated inflammatory pathways.\n\nDisulfiram (DSF), an FDA-approved medication for alcohol use disorder, has been identified as a potent inhibitor of GSDMD-mediated pore formation. Preclinical studies demonstrate that DSF reduces inflammasome activation, decreases cytokine release, and improves metabolic parameters in models of obesity. These findings support the repurposing of DSF as a novel therapeutic strategy in RA, particularly in patients with obesity.\n\nThis 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. A total of 20 participants aged 18-75 years with body mass index (BMI) ≥25 kg\u002Fm² and active disease (Clinical Disease Activity Index \\[CDAI\\] \\>10) will be enrolled and randomized in a 1:1 ratio to receive either DSF (250 mg daily) or placebo. Randomization will be stratified by BMI to ensure balanced allocation.\n\nThe primary objective is to assess the safety and tolerability of DSF in this population. Safety assessments will include adverse event monitoring using Common Terminology Criteria for Adverse Events (CTCAE v5.0), laboratory evaluations (including liver function tests), vital signs, and patient-reported outcomes related to neurotoxicity and quality of life.\n\nSecondary and exploratory objectives include evaluation of systemic inflammation, metabolic function, RA disease activity, and adipose tissue biology. Systemic inflammation will be assessed through circulating cytokines (e.g., IL-1β, IL-6, tumor necrosis factor-α) and immune cell profiling using flow cytometry. 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).\n\nAdipose tissue biopsies will be obtained at baseline and Week 12 to assess inflammasome activation and GSDMD-mediated pathways. Analyses will include evaluation of NLRP3 inflammasome components, caspase-1 activation, GSDMD cleavage, and cytokine release following ex vivo stimulation. These mechanistic studies will provide insight into the biological effects of DSF on adipose tissue inflammation and its relationship to systemic and clinical outcomes.\n\nThis pilot study is designed to generate preliminary data on safety, feasibility, and biological activity to inform the design of future larger clinical trials targeting inflammasome-mediated inflammation in RA",[19,20,21],"Rheumatoid Arthritis","Inflammation","Obesity",[],"INTERVENTIONAL","BASIC_SCIENCE",[26],"PHASE2",{"count":28,"type":29},20,"ESTIMATED",[31,36],{"type":32,"name":33,"description":34,"armGroupLabels":35},"DRUG","Placebo","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.",[33],{"type":32,"name":37,"description":38,"armGroupLabels":39},"Disulfiram (DSF)","Disulfiram will be administered orally at a dose of 250 mg once daily for 12 weeks.",[40],"Disulfiram",[42],{"measure":43,"description":44,"timeFrame":45},"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",[47,51,54,57,60,63,66],{"measure":48,"description":49,"timeFrame":50},"Change in Rheumatoid Arthritis Disease Activity (CDAI)","Change in Clinical Disease Activity Index (CDAI) score from baseline to Week 12.","Baseline and Week 12",{"measure":52,"description":53,"timeFrame":50},"Change in Rheumatoid Arthritis Disease Activity (DAS28-CRP)","Change in Disease Activity Score using 28 joints with C-reactive protein (DAS28-CRP) from baseline to Week 12.",{"measure":55,"description":56,"timeFrame":50},"Change in Insulin Resistance (HOMA-IR)","Change in insulin resistance as measured by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) from baseline to Week 12.",{"measure":58,"description":59,"timeFrame":50},"Change in Body Composition","Change in body composition parameters (fat mass and lean mass) assessed by dual-energy X-ray absorptiometry (DEXA) from baseline to Week 12.",{"measure":61,"description":62,"timeFrame":50},"Change in Adipose Tissue Inflammasome Activation","Change in adipose tissue expression of inflammasome-related markers (including NLRP3, caspase-1 activation, and gasdermin D cleavage) from baseline to Week 12.",{"measure":64,"description":65,"timeFrame":50},"Change in Physical Function","Change in functional status as assessed by the Modified Health Assessment Questionnaire (MDHAQ) from baseline to Week 12.",{"measure":67,"description":68,"timeFrame":50},"Change in Health-Related Quality of Life","Change in health-related quality of life as measured by the Short Form-36 (SF-36) from baseline to Week 12.","ALL","18 Years","75 Years",{"inclusion":73,"exclusion":74,"raw_text":75},[],[],"Inclusion Criteria:\n\nAge 18-75 years Body mass index (BMI) ≥25 kg\u002Fm² Diagnosis of rheumatoid arthritis (RA) according to ACR\u002FEULAR 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\n\n\\-\n\nExclusion Criteria:\n\nSignificant 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\u002Fchronic 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",[77,78],"ADULT","OLDER_ADULT",[80],{"facility":81,"city":82,"state":83,"zip":84,"country":85,"contacts":86,"geoPoint":95},"University of Oklahoma Health Campus","Oklahoma City","Oklahoma","73104","United States",[87,92],{"name":88,"role":89,"phone":90,"email":91},"Natalie Feland, MPH, BSN, RN","CONTACT","405-271-3480","osctr@ouhsc.edu",{"name":93,"role":94},"Beatriz Y Hanaoka, MD, MSc","PRINCIPAL_INVESTIGATOR",{"lat":96,"lon":97},35.46756,-97.51643,[99,101],{"name":93,"role":89,"phone":90,"email":100},"beatriz-hanaoka@ou.edu",{"name":88,"role":89,"phone":90,"email":102},"osctr@ou.edu",[104],{"name":93,"affiliation":13,"role":94},[],[],{"nct_id":4,"conditions":108,"biomarkers":109},[21,19],[],{"nct_id":4,"found":111,"summary":112,"prompt_version":122},true,{"design":113,"status":114,"heading":115,"summary":116,"follow_up":117,"word_count":118,"commitments":119,"compensation":120,"drugs_mentioned":121},"This is an interventional study comparing disulfiram to a placebo. It plans to enroll 20 participants.","completed","Disulfiram for Rheumatoid Arthritis and Obesity","This study is looking at whether disulfiram, an FDA-approved medicine for alcohol use disorder, can help people with rheumatoid arthritis (RA) who also have obesity. RA is a long-lasting disease that causes joint inflammation. Obesity can make RA worse. Researchers believe disulfiram might work by blocking a specific pathway (GSDMD-mediated inflammatory signaling) that causes inflammation. You would receive either disulfiram (250 mg once daily) or a placebo (an inactive pill that looks the same) for 12 weeks. The main goal is to see how safe disulfiram is and if people can tolerate it. To join, you need to be 18-75 years old, have RA with active disease, a BMI of 25 or higher, and be on stable RA medication. The study plans to enroll 20 participants, but its current status is unclear.","Safety and tolerability will be measured from the beginning of the study through Week 12.",132,"You would take a pill once daily for 12 weeks. You would also need to avoid alcohol during the study.","Not stated in the trial record.",[33],"v2"]