Clinical trial NCT04218357: Probenecid as Medication for Alcohol Use Disorder (PROB)
Official title: Probenecid as Pharmacotherapy for Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alcohol Use Disorder
Lead sponsor: Brown University
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 35
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The design is a randomized, within-subject, crossover, double-blind, placebo-controlled human alcohol laboratory study with one oral dose of 2g probenecid or placebo administered in two laboratory sessions.

Detailed description: There will be a total of four study visits. Visit 1 is the screening for eligibility (medical and physical examination). On Visits 2 and 3, participants will undergo an alcohol laboratory session with a one week washout period before administering the alternate therapy. The study will conclude at Visit 4.

Eligibility criteria: Inclusion Criteria:

* Male or female, 21-70 (inclusive) years; women \>7 drinks/week; men \>14 drinks/week;
* meet any DSM-5 criteria score for AUD;
* 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 have a positive urine screen for pregnancy
* CrCl \< 60mL/min
* Taking aspirin (salicylates may reduce effect of probenecid)
* Taking penicillin
* Taking methotrexate (may increase concentration)
* Taking other medications that may interact with probenecid
* History of suicide attempts in the last three years
* Current diagnosis of another substance disorder(s) other than nicotine, as assessed by self-reports and urine toxicology screen at baseline
* History of hypersensitivity to sulfa drugs

Primary outcomes:
measure: Stimulant Effects of Alcohol When Co-administered With Drug or Matching Placebo
timeFrame: Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).
Secondary outcomes:
measure: Sedative Effects of Alcohol When Co-administered With Drug or Matching Placebo
timeFrame: Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).
measure: Alcohol Craving
timeFrame: Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).
Other outcomes:
Locations:
city: Providence
country: United States
facility: Brown University
state: Rhode Island
Study officials:
affiliation: Brown University
name: Carolina L Haass-Koffler, PHARMD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tunstall BJ, Lorrai I, McConnell SA, Gazo KL, Zallar LJ, de Guglielmo G, Hoang I, Haass-Koffler CL, Repunte-Canonigo V, Koob GF, Vendruscolo LF, Sanna PP. Probenecid Reduces Alcohol Drinking in Rodents. Is Pannexin1 a Novel Therapeutic Target for Alcohol Use Disorder? Alcohol Alcohol. 2019 Jan 9;54(5):497-502. doi: 10.1093/alcalc/agz054.
citation: Hornbacher R, Gully BJ, Brown ZE, Brown JC, Magill M, Cioe PA, Swift RM, Sanna PP, Haass-Koffler CL. Probenecid as a pharmacotherapy for alcohol use disorder: A randomized placebo-controlled alcohol interaction trial. Alcohol Clin Exp Res (Hoboken). 2024 Dec;48(12):2391-2403. doi: 10.1111/acer.15470. Epub 2024 Oct 29.