Optimal Dosing, Tolerability, and Initial Efficacy of Diclofenac as a KMO Inhibitor in Individuals With Alcohol Use Disorder

What this Trial Is About

Researchers are investigating the use of diclofenac, a medication already approved for other uses, as a possible treatment for Alcohol Use Disorder (AUD). The study focuses on the kynurenine pathway (KP), which is disrupted by chronic alcohol use, leading to decreased levels of a protective substance called kynurenic acid (KYNA) and increased levels of a harmful substance called quinolinic acid (QUIN). This imbalance is linked to alcohol-related problems, and diclofenac may help restore the balance by inhibiting an enzyme called kynurenine 3-monooxygenase (KMO). In this phase 1 pilot study, 24 participants with AUD will attend four sessions where they will receive one of three doses of diclofenac (50 mg, 75 mg, or 100 mg) or a placebo. The study uses a randomized and quadruple-blind design to compare these treatments. The goal is to find out which dose of diclofenac most effectively increases KYNA levels and to observe effects on QUIN levels, alcohol craving, and mood. Participants will be involved in four sessions over approximately five weeks. Blood samples will be collected to measure changes in KYNA levels from enrollment to the end of the study. Researchers will also evaluate participants' alcohol cravings and negative mood. Safety and tolerability will be monitored throughout the study, which is sponsored by the University of Maryland, Baltimore.

Diclofenac Dose Response Study