Probenecid as Medication for Alcohol Use Disorder (PROB)

Phase 1

Completed

Conditions: Alcohol Use Disorder

Interventions: Drug: Probenecid or placebo single administration

Registration Number: NCT04218357

Lead Sponsor: Brown University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Probenecid	Probenecid or placebo single administration	2g probenecid, one pill by mouth once, for one day
matching placebo	Probenecid or placebo single administration	Placebo, one pill by mouth once, for one day

Primary Outcome Measures

Name	Time	Method
Stimulant Effects of Alcohol When Co-administered With Drug or Matching Placebo	Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).	The stimulant effect of alcohol is assessed using the Biphasic Alcohol Effects Scale (BAES). The BAES is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of 14 items (score) that are rated on a 11-point scale. 7 of the 14 items comprise the stimulation subscale. Individuals are instructed to rate the extent to which alcohol has produced these feelings at the present time from minimum=0 to maximum=10. The subscale of stimulation has a minimum score of 0 (not at all, best outcome) and a maximum score of 70 (high, worse outcome). The scale was validated and published: Martin, C. S., Earleywine, M., Musty, R. E., Perrine, M. W. \& Swift R. M. (1993). Development and Validation of the Biphasic Alcohol Effects Scale. Alcoholism: Clinical and Experimental Research, 17, 140-146.

Secondary Outcome Measures

Name	Time	Method
Sedative Effects of Alcohol When Co-administered With Drug or Matching Placebo	Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).	The sedative effect of alcohol is assessed using the Biphasic Alcohol Effects Scale (BAES). The BAES is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of 14 items (score) that are rated on a 11-point scale. 7 of the 14 items comprise the sedation subscale. Individuals are instructed to rate the extent to which alcohol has produced these feelings at the present time from minimum=0 to maximum=10. The subscale of stimulation has a minimum score of 0 (not at all, best outcome) and a maximum score of 70 (high, worse outcome). The scale was validated and published: Martin, C. S., Earleywine, M., Musty, R. E., Perrine, M. W. \& Swift R. M. (1993). Development and Validation of the Biphasic Alcohol Effects Scale. Alcoholism: Clinical and Experimental Research, 17, 140-146.
Alcohol Craving	Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).	Alcohol craving is assessed using change in the alcohol urge questionnaire (AUQ). The Alcohol Urge Questionnaire (AUQ) consists of eight statements about the respondent's feelings and thoughts about drinking as they are completing the questionnaire (i.e., right now). Drinking refers to various types of alcohol, including beer, wine and liquor. The respondent is asked to respond to each statement about alcohol craving via a 7-item Likert scale ranging from "strongly disagree" to "strongly agree." Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. A total score is computed by averaging the item scores. Minimum score is 7, maximum score is 48. Higher scores reflect greater alcohol craving (worse outcome).