Alcohol Abuse, Alcohol Dependence, Alcoholism
Conditions
Keywords
Randomized Trial, Medication for Heavy Drinking, Dutasteride Treatment
Brief summary
The purpose of this study is to evaluate whether dutasteride is safe and effective for reducing alcohol use in male drinkers who want to stop or reduce their drinking. The investigators hypothesize that at a dosage of 1mg/day, dutasteride will be well tolerated and that, compared to placebo treatment, dutasteride will result in a greater reduction in the amount of alcohol consumed per week. The study sample size is of a pilot scale and is designed to provide additional support for the study hypothesis and provide an estimate of likely effect sizes in order to design a more definitive study.
Interventions
DRUGDutasteride
dutasteride 4 mg loading dose followed by 1 mg daily for 8-week treatment period
DRUGPlacebo
placebo capsules in same number as active drug, daily for 8-week treatment period
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
UConn Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male outpatients age 18 to 65 years * Have an average weekly ethanol consumption of \>24 standard drinks * Be able to read English at the 8th grade or higher level and show no evidence of significant cognitive impairment * Be willing to nominate an individual who will know the patient's whereabouts in order to facilitate follow up during the study * Be willing to provide signed, informed consent to participate in the study (including a willingness to reduce drinking to non-hazardous levels)
Exclusion criteria
* Have a current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation * Have a serious psychiatric illness (e.g., schizophrenia, bipolar disorder, severe or psychotic major depression, organic mood or mental disorders, current eating disorder symptoms, or substantial suicide or violence risk) on the basis of history or psychiatric examination * Have a current diagnosis of drug dependence (other than nicotine or alcohol dependence) * Have a current diagnosis of alcohol dependence who on clinical examination by a physician, are deemed to be too severely alcohol dependent to permit them to participate in a placebo-controlled pilot study * Have a history of hypersensitivity to dutasteride * Current or past 4 month use of finasteride (Propecia), dutasteride (Avodart) or testosterone * Are currently taking psychotropics other than a single antidepressant with stable dose for at least 4 weeks or a non-benzodiazepine sleep medication * Are considered by the investigators to be an unsuitable candidate for receipt of an investigational drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change Number of Standard Drinks Per Week. | Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment) | Change in Average Standard Drinks (14 gr ethanol) per week: last 2 weeks of treatment (wk 7-8) minus baseline average drinking average from baseline 90 day drinking history |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Standard Drinks Per Week - Moderation by Genetic Variation | Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment) | Moderation of primary outcome measure \[change in standard drinks per week from baseline to end point (average weeks 7 and 8 of treatment)\] by genetic variation rs12529 in neuroactive steroid biosynthetic enzyme gene AKR1C (AKR1C3\*2 C-allele associated with alcohol use disorder) |
Countries
United States
Participant flow
Pre-assignment details
4 subjects excluded during screening due to medical or laboratory exclusion (n=3) or current drug dependence (n=1); 4 subjects lost interest in participation following screening and prior to randomization to treatment arm resulting in 37 subjects available for randomization to treatment arm
Participants by arm
| Arm | Count |
|---|---|
| Dutasteride dutasteride (1 mg oral daily dose) for 8-week treatment period
Dutasteride: dutasteride 4 mg loading dose followed by 1 mg daily for 8-week treatment period | 20 |
| Placebo placebo daily for 8-week treatment period
placebo: placebo capsules in same number as active drug, daily for 8-week treatment period | 19 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
Baseline characteristics
| Characteristic | Dutasteride | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 17 Participants | 36 Participants |
| Age, Continuous | 50.95 years STANDARD_DEVIATION 10.21 | 54.95 years STANDARD_DEVIATION 7.44 | 52.90 years STANDARD_DEVIATION 9.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 18 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 18 Participants | 36 Participants |
| Region of Enrollment United States | 20 participants | 19 participants | 39 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 19 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 20 | 9 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 |
Outcome results
Primary
Change Number of Standard Drinks Per Week.
Change in Average Standard Drinks (14 gr ethanol) per week: last 2 weeks of treatment (wk 7-8) minus baseline average drinking average from baseline 90 day drinking history
Time frame: Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride | Change Number of Standard Drinks Per Week. | -26.2 standard drinks per week | Standard Error 4.6 |
| Placebo | Change Number of Standard Drinks Per Week. | -25.5 standard drinks per week | Standard Error 4.1 |
p-value: 0.9t-test, 2 sided
Secondary
Change in Standard Drinks Per Week - Moderation by Genetic Variation
Moderation of primary outcome measure \[change in standard drinks per week from baseline to end point (average weeks 7 and 8 of treatment)\] by genetic variation rs12529 in neuroactive steroid biosynthetic enzyme gene AKR1C (AKR1C3\*2 C-allele associated with alcohol use disorder)
Time frame: Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dutasteride | Change in Standard Drinks Per Week - Moderation by Genetic Variation | -32.4 standard drinks per week | Standard Error 5.4 |
| Placebo | Change in Standard Drinks Per Week - Moderation by Genetic Variation | -31.2 standard drinks per week | Standard Error 13.9 |
| AKR1C3*2 G-carriers + Dutasteride | Change in Standard Drinks Per Week - Moderation by Genetic Variation | 21.8 standard drinks per week | Standard Error 6.9 |
| AKR1C3*2 G-carriers + Placebo | Change in Standard Drinks Per Week - Moderation by Genetic Variation | -22.3 standard drinks per week | Standard Error 3.3 |
p-value: 0.9t-test, 2 sided
p-value: 0.9t-test, 2 sided