Diclofenac as a KMO Inhibitor

NCT06029296 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: HP-00107035
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Keywords

diclofenac

Outcome Measures

Primary Outcomes (1)

• Kynurenic Acid

  Serum levels of Kynurenic Acid

  0-, 60-, 120-, 180-, and 240-minutes after pill administration

Study Arms (2)

Diclofenac

ACTIVE COMPARATOR

Participants will take a single 100mg dose of diclofenac.

Drug: Diclofenac

Placebo

PLACEBO COMPARATOR

Participants will take a single dose of placebo.

Drug: Placebo

Interventions

Diclofenac DRUG

100 mg

Diclofenac

Placebo DRUG

Sugar pill

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

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

Catonsville, Maryland, 21228, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Diclofenac

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Daniel Roche, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 8, 2023
• Study Start: July 31, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)