Probenecid to reduce alcohol craving and consumption

Probenecid, Pannexin 1 Channels for Alcohol Use Disorder

This trial will test whether taking daily probenecid (2 g/day) reduces craving and drinking in adults with moderate-to-severe alcohol use disorder.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Brown University (other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Providence, Rhode Island)
• Trial ID: NCT07118618 on ClinicalTrials.gov

What this trial studies

Over 16 weeks, adults with moderate-to-severe AUD will be randomized in a double-blind, placebo-controlled Phase 2 trial to receive probenecid 2 g/day or matching placebo. The study includes a laboratory phase measuring acute alcohol craving and naturalistic phases tracking craving and real-world alcohol consumption. Participants will have regular clinical visits with safety labs and symptom questionnaires, and outcomes will compare changes in craving and drinking between the probenecid and placebo groups. Screening excludes people with significant liver, kidney, or certain psychiatric conditions and those taking contraindicated medications.

Who should consider this trial

Good fit: Adults (≥18) with moderate-to-severe AUD who drink more than 7 drinks/week for women or 14 drinks/week for men, have BrAC=0.00 at visits, and meet safety lab and clinic visit requirements are ideal candidates.

Not a fit: People who are pregnant or breastfeeding, have significant liver or kidney dysfunction, active psychotic or bipolar disorders, or who take contraindicated medications (for example naltrexone, methotrexate, penicillin, or regular aspirin) are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, probenecid could offer a repurposed medication to help reduce craving and lower alcohol use in people with AUD.

How similar studies have performed: This is a novel repurposing approach with limited prior clinical data for probenecid in AUD, so evidence to date is preliminary rather than established.

Eligibility criteria

Inclusion Criteria:

* • Male or female, ≥18 years.

  * women \>7 drinks/week; men \>14 drinks/week.
  * meet moderate to severe AUD score for DSM-5 criteria.
  * Breath Alcohol Content (BrAC)=0.00 at each visit.
  * in good health as confirmed by medical history, physical examination and lab tests.
  * willing to adhere to the study procedures.
  * understand informed consent and questionnaires in English at an 8th grade level.

Exclusion Criteria:

* • Women who are breastfeeding or positive urine test for pregnancy.

  * clinically significant medical abnormalities: unstable hypertension, clinically significant abnormal EKG, bilirubin \>150% of the upper normal limit, ALT/AST \>300% the UNL, creatinine clearance ≤60 dl/min
  * meet DSM-5 criteria for a diagnosis of schizophrenia, bipolar disorder, or other psychoses
  * medications that reduce alcohol consumption (naltrexone, disulfiram).
  * use aspirin (salicylates may reduce effect of probenecid), penicillin, methotrexate (may increase concentration).
  * history of suicide attempts in the last three years.
  * current diagnosis of a moderate or severe cannabis use disorder as assessed by self-report, SCID-E for SUD, and urine toxicology screen at baseline.
  * current diagnosis of another substance disorder at any severity, other than nicotine, as assessed by self-report, SCID-E for SUD, and urine toxicology screen at baseline.
  * current use of medications that may interact with probenecid.
  * history of hypersensitivity to sulfa drugs.

Where this trial is running

Providence, Rhode Island

• Brown University — Providence, Rhode Island, United States (RECRUITING)

Study contacts

• Principal investigator: Carolina Haass-Koffler, PharmD, PhD — Brown Univiversity
• Study coordinator: Brian Gully, MA

Conditions: Alcohol Use Disorder, Alcohol Consumption, Craving, AUD, Probenecid, Alcohol