Dutasteride Treatment for the Reduction of Heavy Drinking in Men

Study Overview
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Brief Summary
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This study will examine the safety and potential benefit of the medication dutasteride to help men reduce or stop drinking alcohol.

Detailed Description
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Extensive preclinical studies indicate that neuroactive steroids medicate important effects of alcohol and support the examination of neuroactive steroid modulators as treatment options for alcohol use problems. Dutasteride, a widely prescribed medication for benign prostatic hypertrophy, blocks a key step in the production of neuroactive steroids and represents a promising candidate for treatment of alcohol use disorders. This study will use a 12-week randomized placebo controlled design to examine the safety and efficacy of dutasteride to reduce drinking among a sample of 160 men with hazardous levels of alcohol use. It will additionally examine the potential moderation of dutasteride treatment effects by a common missense polymorphism in a neuroactive steroid biosynthetic enzyme that we have previously reported to be associated with alcohol dependence. Identification of genetic predictors of medication response offers the potential for matching alcohol treatment medications with those most likely to respond.

Official Title
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Dutasteride Treatment for the Reduction of Heavy Drinking

Conditions
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Alcoholism, Alcohol Abuse, Alcohol Dependence

Intervention / Treatment
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* Drug: Dutasteride
* Drug: sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: an average weekly ethanol consumption of at least 24 standard drinks; be able to read English at the 8th grade or higher level; no evidence of significant cognitive impairment; be willing to provide signed, informed consent to participate in the study (including a willingness to stop or reduce drinking to non-hazardous levels); be willing to nominate an individual who will know the patient's whereabouts to facilitate follow up during the study Exclusion Criteria: history of significant alcohol withdrawal symptoms (e.g. substantial tremor, autonomic changes, perceptual distortions, seizures, delirium, or hallucinations); current Diagnostic and Statistical Manual Version IV (DSM-IV) 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 study (e.g. evidence of serious adverse medical or psychiatric effects that are exacerbated by heavy drinking and would, for safety reasons, lead the physician to urge the patient to be totally abstinent and engage in an empirically supported treatment). current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation,(we will not exclude patients with hypertension, diabetes mellitus, asthma or other common medical conditions, if these are adequately controlled and the patient has an ongoing relationship with a primary care provider) serious psychiatric illness on the basis of history or psychiatric examination (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, organic mental disorder, current clinically significant eating disorder, or substantial suicide or violence risk); current DSM-IV diagnosis of drug dependence (other than nicotine dependence); currently taking psychotropics other than medication for depression/anxiety disorder (with stable dose for at least 4 weeks),medications for treatment of Attention Deficit/Hyperactivity Disorder (with stable dose for at least 4 weeks), a non-benzodiazepine sleep medication or a low dose of benzodiazepine equivalent to 2 mg clonazepam or lorazepam per day; are considered by the investigators to be an unsuitable candidate for receipt of an investigational drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dutasteride<br>4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. | Drug: Dutasteride<br> <br> * Other names: Avodart;|
| Placebo Comparator: Sugar Pill<br>Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. | Drug: sugar pill<br> <br> * Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heavy Drinking Days Per Week | Number of days / study week with 5 or more drinks consumed | 12-week treatment period | 
| Drinks Per Week | Total number of drinks aggregated by week | 12-week treatment period | 
| Number of Participants With no Heavy Drinking Days | Number of participants with no heavy drinking days (days with 5 or more drinks) during the last 4 weeks of treatment. | Last 4 weeks of treatment | 
| Number of Participants With no Hazardous Drinking | Number of participants with no hazardous drinking (not more than 4 drinks on one day and not more than 14 drinks per week) during the last 4 weeks of treatment. | Last 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HDD/ Week by Treatment Group and AKR1C3*2 Genotype | Change in Number of days / week with 5 or more drinks consumed contrasting AKR1C3*2 CC vs. G-carrier genotype and treatment group | 12-week treatment period | 
| Carbohydrate-deficient Transferrin | Carbohydrate-deficient transferrin (CDT) at end of treatment as percentage of baseline. Serum CDT is a biochemical measure of heavy alcohol use. | end of 12-week treatment vs. baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuroactive steroids