Dutasteride Treatment for the Reduction of Heavy Drinking in Men

• Sponsor: UConn Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01758523
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 189
• Location: 1
• Arms: 2
• Duration (Months): 61.9
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Alcoholism; Alcohol Abuse; Alcohol Dependence	Drug: Dutasteride; Drug: sugar pill	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dutasteride Treatment for the Reduction of Heavy Drinking
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Feb 28, 2018
• Actual Study Completion Date: Feb 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dutasteride 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks.	Drug: Dutasteride; Other Names: Avodart
Placebo Comparator: Sugar Pill 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; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. Heavy Drinking Days Per Week [12-week treatment period]

   Number of days / study week with 5 or more drinks consumed

2. Drinks Per Week [12-week treatment period]

   Total number of drinks aggregated by week

3. Number of Participants With no Heavy Drinking Days [Last 4 weeks of treatment]

   Number of participants with no heavy drinking days (days with 5 or more drinks) during the last 4 weeks of treatment.

4. Number of Participants With no Hazardous Drinking [Last 4 weeks of treatment]

   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.

Secondary Outcome Measures

1. HDD/ Week by Treatment Group and AKR1C3*2 Genotype [12-week treatment period]

   Change in Number of days / week with 5 or more drinks consumed contrasting AKR1C3*2 CC vs. G-carrier genotype and treatment group

2. Carbohydrate-deficient Transferrin [end of 12-week treatment vs. baseline]

   Carbohydrate-deficient transferrin (CDT) at end of treatment as percentage of baseline. Serum CDT is a biochemical measure of heavy alcohol use.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Connecticut Health Center	Farmington	Connecticut	United States	06030

Sponsors and Collaborators

• UConn Health
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Jonathan Covault, M.D., PhD., UConn Health

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 10, 2017

More Information

Publications

None provided.

• Responsible Party: Jonathan Covault, Professor of Psychiatry, UConn Health
• ClinicalTrials.gov Identifier: NCT01758523
• Other Study ID Numbers: 13-056-2; 2P60AA003510
• First Posted: Jan 1, 2013
• Last Update Posted: Apr 26, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Jonathan Covault, Professor of Psychiatry, UConn Health: neuroactive steroids
• Additional relevant MeSH terms: Alcoholism; Dutasteride

Study Results

Participant Flow

Pre-assignment Detail	47 subjects not randomized: 23 excluded at in person screening visit; 24 subjects withdrew prior to randomization

Arm/Group Title	Dutasteride	Sugar Pill
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Period Title: Overall Study
STARTED	74	68
Attended >/= 1 Visit Post-randomization	68	67
COMPLETED	53	54
NOT COMPLETED	21	14

Baseline Characteristics

Arm/Group Title	Dutasteride	Sugar Pill	Total
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Total of all reporting groups
Overall Participants	68	67	135
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	64 94.1%	62 92.5%	126 93.3%
>=65 years	4 5.9%	5 7.5%	9 6.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.0 (7.9)	53.1 (9.4)	53.0 (8.6)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	68 100%	67 100%	135 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.5%	0 0%	1 0.7%
Not Hispanic or Latino	67 98.5%	67 100%	134 99.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.5%	1 1.5%	2 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1.5%	1 1.5%	2 1.5%
White	66 97.1%	65 97%	131 97%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	68 100%	67 100%	135 100%
Heavy Drinking Days (HDD)/wk (heavy drinking days / week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [heavy drinking days / week]	5.2 (2.2)	5.2 (2.1)	5.2 (2.1)
Drinks/week (drinks/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [drinks/week]	48.8 (24)	47.3 (20.4)	48.0 (22.2)
AbstinentDays/week (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	0.67 (1.1)	0.62 (1.1)	0.64 (1.1)
DSM-IV Alcohol Dependence criteria (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.3 (1.6)	4.0 (1.6)	4.2 (1.6)
Short Inventory of Problems (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	17.2 (8.2)	16.8 (8.8)	17.0 (8.4)
Smoker (Count of Participants)
Count of Participants [Participants]	12 17.6%	12 17.9%	24 17.8%

Outcome Measures

1. Primary Outcome

Title	Heavy Drinking Days Per Week
Description	Number of days / study week with 5 or more drinks consumed
Time Frame	12-week treatment period

Outcome Measure Data

Analysis Population Description

Modified Intention to Treat (ITT) all subjects who attended one or more post-randomization visit.

Arm/Group Title	Dutasteride	Sugar Pill
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Measure Participants	68	67
Mean (Standard Error) [heavy drinking days/week]	1.75 (0.33)	2.67 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Sugar Pill
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Drinks Per Week
Description	Total number of drinks aggregated by week
Time Frame	12-week treatment period

Outcome Measure Data

Analysis Population Description

Modified ITT (all subjects who attended one or more post-randomization visit)

Arm/Group Title	Dutasteride	Sugar Pill
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Measure Participants	68	67
Mean (Standard Error) [drinks/week]	22.0 (2.6)	27.2 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Sugar Pill
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.028
	Comments
	Method	Mixed Models Analysis
	Comments

3. Primary Outcome

Title	Number of Participants With no Heavy Drinking Days
Description	Number of participants with no heavy drinking days (days with 5 or more drinks) during the last 4 weeks of treatment.
Time Frame	Last 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

Per protocol 12-week completer

Arm/Group Title	Dutasteride	Sugar Pill
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Measure Participants	53	54
Count of Participants [Participants]	16 23.5%	8 11.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Sugar Pill
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.49
	Confidence Interval	(2-Sided) 95%; 0.96 to 6.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Participants With no Hazardous Drinking
Description	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.
Time Frame	Last 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

Per protocol 12 week treatment completers

Arm/Group Title	Dutasteride	Sugar Pill
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Measure Participants	53	54
Count of Participants [Participants]	13 19.1%	3 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Sugar Pill
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.5
	Confidence Interval	(2-Sided) 95%; 1.5 to 20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	HDD/ Week by Treatment Group and AKR1C3*2 Genotype
Description	Change in Number of days / week with 5 or more drinks consumed contrasting AKR1C3*2 CC vs. G-carrier genotype and treatment group
Time Frame	12-week treatment period

Outcome Measure Data

Analysis Population Description

Modified ITT (all subjects who attended one or more post-randomization visit)

Arm/Group Title	Dutasteride - AKR1C3*2 CC	Sugar Pill - AKR1C3*2 CC	Dutasteride - AKR1C3*2 G-carrier	Sugar Pill - AKR1C3*2 G-carrier
Arm/Group Description	dutasteride treated AKR1C3*2 CC genotype subjects	placebo treated AKR1C3*2 CC genotype subjects	dutasteride treated AKR1C3*2 G-carrier genotype subjects	placebo treated AKR1C3*2 G-carrier genotype subjects
Measure Participants	19	25	49	42
Mean (Standard Error) [heavy drinking days/week]	1.06 (0.48)	2.9 (0.53)	2.05 (0.42)	2.5 (0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Sugar Pill, Dutasteride - AKR1C3*2 G-carrier, Sugar Pill - AKR1C3*2 G-carrier
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments	significance for drug x AKR1C3*2 G-carrier genotype
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Carbohydrate-deficient Transferrin
Description	Carbohydrate-deficient transferrin (CDT) at end of treatment as percentage of baseline. Serum CDT is a biochemical measure of heavy alcohol use.
Time Frame	end of 12-week treatment vs. baseline

Outcome Measure Data

Analysis Population Description

Per protocol 12-week completers (serum sample not available for 1 placebo subject).

Arm/Group Title	Dutasteride	Sugar Pill
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Measure Participants	53	53
Mean (Standard Error) [percentage of baseline CDT]	94 (3.8)	107 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Sugar Pill
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Bi-weekly during 12-week active treatment then bi-monthly for 6 months
Adverse Event Reporting Description	At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Arm/Group Title	Dutasteride		Sugar Pill
Arm/Group Description	4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride		Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
All Cause Mortality
	Dutasteride		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/67 (0%)
Serious Adverse Events
	Dutasteride		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/68 (5.9%)		2/67 (3%)
Infections and infestations
Tonsillar abscess	1/68 (1.5%)		0/67 (0%)
Musculoskeletal and connective tissue disorders
Chronic back pain	0/68 (0%)		1/67 (1.5%)
Nervous system disorders
alcohol withdrawal	2/68 (2.9%)		1/67 (1.5%)
Respiratory, thoracic and mediastinal disorders
COPD exacerbation	1/68 (1.5%)		0/67 (0%)
Other (Not Including Serious) Adverse Events
	Dutasteride		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/68 (54.4%)		27/67 (40.3%)
Gastrointestinal disorders
Stomach discomfort	11/68 (16.2%)		3/67 (4.5%)
Nausea	4/68 (5.9%)		5/67 (7.5%)
General disorders
Headache	10/68 (14.7%)		11/67 (16.4%)
Fatigue	5/68 (7.4%)		7/67 (10.4%)
Sleep disturbance	5/68 (7.4%)		3/67 (4.5%)
Musculoskeletal and connective tissue disorders
Muscle or joint pain	11/68 (16.2%)		7/67 (10.4%)
Reproductive system and breast disorders
Reduced Libido	6/68 (8.8%)		0/67 (0%)
Impotence	4/68 (5.9%)		2/67 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.