Exploring the effects of diclofenac on alcohol use disorder
Optimal Dosing, Tolerability, and Initial Efficacy of Diclofenac as a KMO Inhibitor in Individuals With Alcohol Use Disorder
This study is testing if the pain reliever diclofenac can help people aged 21-65 with alcohol use disorder by trying to improve their brain chemistry.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 21 Years to 65 Years |
| Sex | All |
| Sponsor | University of Maryland, Baltimore Academic / other |
| Drugs / interventions | methotrexate |
| Locations | 1 site (Catonsville, Maryland) |
| Trial ID | NCT06636227 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the efficacy of diclofenac, a nonsteroidal anti-inflammatory drug, in treating alcohol use disorder (AUD) by targeting the kynurenine pathway, which is disrupted by chronic alcohol consumption. Participants aged 21-65 who meet the DSM-5 criteria for AUD will be administered varying doses of diclofenac or a placebo to assess its impact on metabolite levels associated with addiction neurobiology. The study aims to restore the balance of neuroprotective and neurotoxic metabolites in individuals with AUD, potentially leading to improved treatment outcomes. The trial is conducted at the Maryland Psychiatric Research Center.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 21-65 who meet the DSM-5 criteria for alcohol use disorder and have a history of heavy drinking.
Not a fit: Patients currently undergoing treatment for alcohol use disorder or those with severe substance use disorders other than alcohol may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a novel pharmacological option for individuals struggling with alcohol use disorder.
How similar studies have performed: While the approach of targeting the kynurenine pathway is novel, other studies have explored pharmacological interventions for AUD with varying degrees of success.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age 21-65 * Meet DSM-5 diagnostic criteria for current AUD of any severity (Mild, Moderate, or Severe) * In the 30-day period before enrollment, consume \> 14 and \> 7 standard drinks per week for men and women, respectively * In the 30-day period before enrollment, engage in heavy drinking (5 or more drinks for men, 4 or more drinks for women) ≥ 5 times per month Exclusion Criteria: * Currently in treatment, a history of treatment within the 30 days before enrollment, or currently seeking immediate treatment for AUD * Current (last 12 months) DSM-5 diagnosis of SUD for any psychoactive substances other than alcohol, nicotine, and cannabis (cannabis use disorder, mild severity allowed; moderate and severe excluded) * Currently prescribed a psychotropic medication for the treatment of schizophrenia spectrum and other psychotic disorders, bipolar and related disorders * Lifetime DSM-5 diagnosis of schizophrenia spectrum and other psychotic disorders and bipolar and related disorders * Positive urine toxicology screen for the following substances: cocaine, opiates, amphetamines, methamphetamine, phencyclidine, barbiturates, benzodiazepine, methadone, and tricyclic antidepressants * Self-reported current daily use of opioids (including prescribed) * If female: pregnant, nursing, or with reproductive potential who refuses to use reliable methods of birth control throughout the study * Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised * Any autoimmune disorder, inflammatory disorder, hypercoagulable state, cardiovascular disease or other medical condition (e.g., any cardiac, renal, or liver disease, uncontrolled hypertension, or diabetes) that may interfere with safe study participation and/or study aims. Specific examples of exclusionary medical conditions include but are not limited to: 1. Any lifetime history of 1) serious GI conditions, including ulcer disease, gastrointestinal bleeding, and clinically significant gastritis, or, 2) serious cardiovascular conditions, including heart failure, myocardial infarction, stroke, pulmonary embolism, blood clots, deep vein thrombosis, or clotting disorder, 3) liver disease or impaired liver function, and 4) renal disease or insufficiency 2. Current uncontrolled hypertension 3. AST and ALT \> four times the upper limit of the normal range, or albumin, GFR, BUN, or creatinine 15% \> the upper limit of the normal range 4. Clinically significant ECG findings, including clinically significant arrhythmia, atrioventricular block, prolonged QTc interval, or enlarged or hypertrophic heart 5. Serious brain conditions, including epilepsy, dementia and neurodegenerative diseases, traumatic brain injury (TBI), etc. TBI exclusionary criteria include: suffered a mild or moderate TBI within the last 12 months, a severe TBI at any point in their life, or a moderate TBI before the age of 12 * Attempted suicide in the past 3 years and/or serious suicidal intention or plan within the past year * Currently on prescription medication that contraindicates use of diclofenac, including but not necessarily limited to: oral corticosteroids, anticoagulants, lithium, warfarin, aspirin (daily use), methotrexate, cyclosporine, ACE-inhibitors, diuretics like furosemide and thiazides, and any medication that significantly influences CYP2C9 enzyme activity (e.g., rifampin, voriconazole). * Previously known hypersensitivity, including gastroenteritis, asthma, and allergic-type reactions, to any NSAID and/or aspirin * Current daily use of any NSAID or regular pattern of near daily use within the past three months, regular use of a prebiotic or probiotic supplement and/or any antibiotic, prebiotic, or probiotic use within the last month * Any other circumstances that, in the opinion of the investigators, compromises participant safety, ability of the investigators to conduct the study as designed, and/or study integrity * Current or recent (within 3 months) participation in a clinical trial involving medication administration * Has below a 6th grade reading level * Within the last 3 months, tested positive for COVID-19 (i.e. the SARS-CoV-2 virus) and experienced common related symptoms
Where this trial is running
Catonsville, Maryland
- Maryland Psychiatric Research Center — Catonsville, Maryland, United States (Recruiting)
Study contacts
- Study coordinator: Mathew Glassman, MS
- Email: mglassman@som.umaryland.edu
- Phone: 410-402-6411
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.