Diclofenac Dose Response Study

Part of paid clinical trials in Catonsville, Maryland.

Sponsor
University of Maryland, Baltimore
Study ID
NCT06636227
Phase
PHASE1
Status
Recruiting
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Conditions

  • Alcohol Use Disorder (AUD)
  • Alcohol-Related Disorders

Eligibility Criteria

Sex
ALL
Age
21 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Diclofenac 100mg — DRUG
    Diclofenac 100mg
  • Diclofenac 75mg — DRUG
    Diclofenac 75mg
  • Diclofenac 50mg — DRUG
    Diclofenac 50mg
  • Placebo control — DRUG
    Placebo control

Study Details

The development of efficacious medications for AUD remains a high research priority with current emphases on identifying novel molecular targets and efficiently screening new compounds. Pharmacological modulation of the kynurenine pathway (KP) represents a promising novel target for AUD. The KP is a complex enzymatic cascade with each step producing biologically active metabolites that are critically involved in diverse physiological and pathological processes. Chronic alcohol exposure produces dysregulation of the KP, particularly as evidenced by decreased levels of the neuroprotective metabolite kynurenic acid (KYNA) and increased levels of the neurotoxic metabolite quinolinic acid (QUIN). This metabolic shift is associated with various alcohol-related pathologies in animals and humans. Thus, a medication that targets the KP to restore KYNA and attenuate QUIN levels may be an effective treatment for AUD. The enzyme kynurenine 3- monooxygenase (KMO) is a major gatekeeper of the KP and resultant KYNA levels. KMO inhibition shifts the KP towards KYNA production in brain and away from QUIN production. Critically, KMO inhibition in rodents, through its increase in brain KYNA levels, decreases alcohol self-administration, preference, cue-reactivity, and relapse behaviors. However, KMO-inhibitors have not been tested in humans because of presumed lack of availability. Diclofenac is an FDA-approved Non-Steroidal Anti-Inflammatory Drug that was recently discovered to inhibit KMO activity. Consistent with KMO inhibition, diclofenac increases KYNA levels in the brain and periphery of rodents. However, it remains unknown whether diclofenac increases KYNA levels and affects alcohol-related behaviors in humans at approved, safe dosages. Investigators propose to conduct a human laboratory pilot study to test whether diclofenac can increase KYNA in individuals with AUD, and if so, which of 3 doses (50, 75, or 100 mg) most effectively increases KYNA. Individuals with AUD (n = 24) will complete four sessions where they receive diclofenac (50, 75, or 100 mg) or placebo. Investigators will examine increases in KYA levels and will also assess QUIN levels, alcohol craving, and negative mood.

Key Dates

Start date
Dec 1, 2024
Status verified
Feb 2026
Primary completion
May 31, 2026
Completion
Aug 31, 2026

Study Design

Enrollment
24 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Placebo Comparator: Placebo
    Placebo arm
  • Active Comparator: Diclofenac 50mg
    In this arm participants will receive 50mg of Diclofenac
  • Active Comparator: Diclofenac 75mg
    In this arm participants will receive 75mg of Diclofenac
  • Active Comparator: Diclofenac 100mg
    In this arm participants will receive 100mg of Diclofenac

Primary Outcome Measure

Change in blood kynurenic acid (KYNA) levels [ Time Frame: From enrollment to the end of session 4 (approximately 5 weeks) ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Maryland Psychiatric Research CenterCatonsvilleMaryland21248
Mathew Glassman, MS
[email protected]
410-402-6411

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By research site
Maryland Psychiatric Research Center· Catonsville, MD

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