Diclofenac as a KMO Inhibitor

Phase

Condition

Alcohol Use Disorder

Substance Abuse

Alcohol Dependence

Treatment

Placebo

Diclofenac

Clinical Study ID

NCT06029296

HP-00107035

Ages 21-65
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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

Exclusion

Exclusion Criteria:

Lifetime DSM-5 diagnosis of schizophrenia spectrum and other psychotic disorders andbipolar 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 ClinicalInstitute Withdrawal Assessment for Alcohol-Revised
If female: pregnant, nursing, or with reproductive potential who refuses to usereliable methods of birth control throughout the study
Any autoimmune disorder, inflammatory disorder, or medical condition that mayinterfere 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 planwithin 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, andallergic-type reactions, to any NSAID and/or aspirin
Current daily use of any NSAID or regular pattern of near daily use within the pastthree months, regular use of a prebiotic or probiotic supplement and/or anyantibiotic, prebiotic, or probiotic use within the last month
Any lifetime history of ulcer disease, gastritis, gastroenteritis, orgastrointestinal bleeding
Current or recent (within 3 months) participation in a clinical trial involvingmedication 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 substancesother than alcohol and nicotine
Currently prescribed a psychotropic medication for the treatment of schizophreniaspectrum 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, compromisesparticipant safety, ability of the investigators to conduct the study as designed,and/or study integrity

Study Design