Probenecid for Alcoholism

(PROB2 Trial)

Overseen By Brian Gully, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brown University

Must not be taking: Naltrexone, Disulfiram, Aspirin, others

Disqualifiers: Pregnancy, Schizophrenia, Bipolar, Cannabis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether probenecid can reduce cravings and alcohol consumption in individuals with alcohol use disorder (AUD). It compares probenecid to a placebo (a harmless pill with no active drug) over 16 weeks. Suitable candidates for this trial include women who consume more than 7 drinks per week and men who consume more than 14 drinks per week, and who meet a moderate to severe AUD profile. Participants should be in good health and willing to attend regular study visits. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Is there any evidence suggesting that probenecid is likely to be safe for humans?

Research has shown that probenecid is safe and generally well-tolerated when taken with alcohol. Studies suggest it can help reduce the urge to drink without causing serious side effects. Participants in previous studies did not experience more significant negative effects than those who took a placebo, which is a harmless pill. The FDA has already approved probenecid for other uses, supporting its safety in humans. However, probenecid is not yet approved specifically for treating alcohol use disorder. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Probenecid is unique because it offers a potential new approach to treating alcoholism by targeting uric acid transporters, which is different from most current treatments that focus on altering neurotransmitter activity in the brain. Unlike standard medications like naltrexone, acamprosate, and disulfiram, which primarily manage cravings or create unpleasant reactions to alcohol, Probenecid's mechanism could offer an innovative pathway to reduce alcohol dependence. Researchers are excited about this treatment because it might provide an alternative for individuals who do not respond well to existing medications, potentially broadening the options for effective management of alcoholism.

What evidence suggests that probenecid might be an effective treatment for alcoholism?

Research has shown that probenecid might help reduce both the urge to drink alcohol and the amount consumed. In this trial, participants will receive either probenecid or a placebo, which contains no active medicine. One study found that people taking probenecid experienced less craving for alcohol than those taking a placebo. Animal studies also found that probenecid lowered both regular and binge drinking in rats and mice, suggesting a similar effect might occur in humans. While these results are promising, further research is needed to fully understand its effectiveness in treating alcohol use disorder. ^{1 2 3 4 6}

Who Is on the Research Team?

Carolina Haass-Koffler, PharmD, PhD

Principal Investigator

Brown Univiversity

Are You a Good Fit for This Trial?

Inclusion Criteria

I am 18 years old or older.

I drink no more than 7 drinks a week (if female) or 14 drinks a week (if male).

Meet moderate to severe AUD score for DSM-5 criteria

Exclusion Criteria

I use aspirin, penicillin, or methotrexate.

History of suicide attempts in the last three years

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Laboratory Phase

Participants undergo an alcohol cue-reactivity procedure to assess acute alcohol craving using the alcohol urge questionnaire (AUQ)

5 weeks

Naturalistic Phase

Participants are monitored for alcohol craving and consumption using the Obsessive Compulsive Drinking Scale (OCDS) and timeline follow-back (TLFB) method

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Probenecid

How Is the Trial Designed?

Group I: Study drug Experimental Treatment 1 Intervention

Probenecid 2gr oral

Group II: Placebo Placebo Group 1 Intervention

Placebo inactive

Who Is Running the Clinical Trial?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11963961/

Probenecid as a pharmacotherapy for alcohol use disorder

Our findings strongly indicate that probenecid, when co-administered with alcohol, was safe, well-tolerated, and reduced craving in individuals who regularly ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04218357

Probenecid as Medication for Alcohol Use Disorder (PROB)

Higher scores reflect greater alcohol craving (worse outcome). Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of ...

3.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/abs/10.1111/acer.15470

Probenecid as a pharmacotherapy for alcohol use disorder ...

Probenecid, compared to placebo, significantly decreased alcohol craving during the alcohol ascending limb. Inflammatory biomarkers, cognitive ...

4.

academic.oup.com

academic.oup.com/alcalc/article/54/5/497/5571632

Probenecid Reduces Alcohol Drinking in Rodents. Is ...

In conclusion, we showed that probenecid reduces both dependent and nondependent alcohol drinking in rats and binge-like drinking in mice. These ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31535696/

Probenecid Reduces Alcohol Drinking in Rodents ... - PubMed

Probenecid reduced alcohol intake in both dependent and nondependent rats and in the DID paradigm in mice without affecting water or saccharin intake.

6.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0741832923002653

Evaluating the readability of online patient-facing ...

The goal of this study was to assess the readability of online resources pertaining to Alcohol Use Disorder (AUD) as perceived by patients seeking treatment.