DKMOI: Diclofenac as a KMO Inhibitor

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06029296

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Diclofenac Drug: Placebo	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Proof of Concept: Diclofenac as a KMO Inhibitor in Individuals With Alcohol Use Disorder

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Diclofenac Participants will take a single 100mg dose of diclofenac.	Drug: Diclofenac 100 mg
Placebo Comparator: Placebo Participants will take a single dose of placebo.	Drug: Placebo Sugar pill

Arm

Intervention/Treatment

Active Comparator: Diclofenac

Participants will take a single 100mg dose of diclofenac.

Drug: Diclofenac

100 mg

Placebo Comparator: Placebo

Participants will take a single dose of placebo.

Drug: Placebo

Sugar pill

Outcome Measures

Primary Outcome Measures

Kynurenic Acid [0-, 60-, 120-, 180-, and 240-minutes after pill administration]
Serum levels of Kynurenic Acid

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP)	Catonsville	Maryland	United States	21228

Sponsors and Collaborators

University of Maryland, Baltimore

Investigators

Principal Investigator: Daniel Roche, PhD, University of Maryland School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Maryland, Baltimore

ClinicalTrials.gov Identifier:

NCT06029296

Other Study ID Numbers:

HP-00107035

First Posted:

Sep 8, 2023

Last Update Posted:

Sep 8, 2023

Last Verified:

Aug 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by University of Maryland, Baltimore

diclofenac

Additional relevant MeSH terms:

Alcoholism

Alcohol Drinking

Diclofenac

Study Results

No Results Posted as of Sep 8, 2023