Alcohol Use Disorder
Conditions
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.
Interventions
DRUGProbenecid or placebo single administration
study drug administration with alcohol in the laboratory
Sponsors
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Sample Placebo, then probenecid one pill by mouth once, for one day or Probenecid then placebo one pill by mouth once, for one day | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 1st Allocation | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Sample |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Diagnosis of alcohol use disorder (AUD) by SCID-5 Mild AUD | 12 Participants |
| Diagnosis of alcohol use disorder (AUD) by SCID-5 Moderate AUD | 8 Participants |
| Diagnosis of alcohol use disorder (AUD) by SCID-5 no AUD | 9 Participants |
| Diagnosis of alcohol use disorder (AUD) by SCID-5 Severe AUD | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 34 |
| other Total, other adverse events | 0 / 35 | 0 / 34 |
| serious Total, serious adverse events | 0 / 35 | 0 / 34 |
Outcome results
Primary
Stimulant Effects of Alcohol When Co-administered With Drug or Matching Placebo
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.
Time frame: Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Stimulant Effects of Alcohol When Co-administered With Drug or Matching Placebo | Ascending alcohol BrAC | 28.23 scores on scale | Standard Deviation 21.82 |
| Matching Placebo | Stimulant Effects of Alcohol When Co-administered With Drug or Matching Placebo | Descending alcohol BrAC | 20.57 scores on scale | Standard Deviation 18.95 |
| Probenecid | Stimulant Effects of Alcohol When Co-administered With Drug or Matching Placebo | Ascending alcohol BrAC | 25.26 scores on scale | Standard Deviation 20.66 |
| Probenecid | Stimulant Effects of Alcohol When Co-administered With Drug or Matching Placebo | Descending alcohol BrAC | 19.56 scores on scale | Standard Deviation 20.33 |
Secondary
Alcohol Craving
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).
Time frame: Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Alcohol Craving | Ascending limb of BrAC | 23.09 score on scale | Standard Deviation 13.23 |
| Matching Placebo | Alcohol Craving | Descending limb of BrAC | 19.63 score on scale | Standard Deviation 12.04 |
| Probenecid | Alcohol Craving | Ascending limb of BrAC | 17.24 score on scale | Standard Deviation 10.47 |
| Probenecid | Alcohol Craving | Descending limb of BrAC | 18.38 score on scale | Standard Deviation 12.29 |
Comparison: All outcomes were assessed in real-time in the laboratory testing probenecid compared to placebo condition during the alcohol administration procedure.p-value: 0.05GEE
Secondary
Sedative Effects of Alcohol When Co-administered With Drug or Matching Placebo
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.
Time frame: Twice at each laboratory session, visits 2 and 3, during the ascending and descending phase of alcohol administration (BrAC).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Sedative Effects of Alcohol When Co-administered With Drug or Matching Placebo | Ascending limb of BrAC | 16.02 scores on scale | Standard Deviation 14.21 |
| Matching Placebo | Sedative Effects of Alcohol When Co-administered With Drug or Matching Placebo | Descending limb of BrAC | 16.26 scores on scale | Standard Deviation 15.27 |
| Probenecid | Sedative Effects of Alcohol When Co-administered With Drug or Matching Placebo | Ascending limb of BrAC | 16.79 scores on scale | Standard Deviation 15.17 |
| Probenecid | Sedative Effects of Alcohol When Co-administered With Drug or Matching Placebo | Descending limb of BrAC | 16.50 scores on scale | Standard Deviation 15.15 |