Diclofenac as a KMO Inhibitor

NCT ID: NCT06029296

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2026-01-31

Brief Summary

This mechanistic, proof of concept laboratory study will test the pharmacological properties of diclofenac in individuals with AUD. Participants will complete two sessions in which they will receive a single dose of diclofenac (100 mg) or matched placebo in a randomized and double blind fashion. The primary aim is to assess whether this dose of diclofenac, vs. placebo, increases circulating levels of kynurenic acid. This finding would provide evidence that diclofenac (100 mg) inhibits the kynurenine 3-monooxygenase enzyme.

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Diclofenac

Participants will take a single 100mg dose of diclofenac.

Group Type: ACTIVE_COMPARATOR

Diclofenac

Intervention Type: DRUG

100 mg

Placebo

Participants will take a single dose of placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sugar pill

Interventions

Diclofenac

100 mg

Intervention Type: DRUG

Placebo

Sugar pill

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ages 21-65
• Meet DSM-5 diagnostic criteria for AUD of any severity (Mild, Moderate, or Severe)

Exclusion Criteria

• 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 daily use of opioids (including prescribed)
• Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised
• If female: pregnant, nursing, or with reproductive potential who refuses to use reliable methods of birth control throughout the study
• Any autoimmune disorder, inflammatory disorder, or medical condition that may interfere with safe study participation and/or study aims (e.g., any cardiac, renal, or liver disease, uncontrolled hypertension, or diabetes)
• 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, and diuretics like furosemide and thiazides
• 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 lifetime history of ulcer disease, gastritis, gastroenteritis, or gastrointestinal bleeding
• Current or recent (within 3 months) participation in a clinical trial involving medication administration
• 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 and nicotine
• Currently prescribed a psychotropic medication for the treatment of schizophrenia spectrum and other psychotic disorders, bipolar and related disorders
• 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
• Suffered a mild or moderate traumatic brain injury (TBI) within the last 12 months, a severe TBI at any point in their life, or a moderate TBI before the age of 12
• 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
• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Daniel Roche

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Roche, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP)

Catonsville, Maryland, United States

Countries

United States

Other Identifiers

HP-00107035

Identifier Type: -

Identifier Source: org_study_id