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Trial record 77 of 117 for:    DUTASTERIDE

Pharmacogenetics of Alcohol: Treatment Implications

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00734656
Recruitment Status : Completed
First Posted : August 14, 2008
Results First Posted : March 27, 2012
Last Update Posted : March 28, 2012
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Jonathan Covault, UConn Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Conditions Alcohol Related Disorders
Alcoholism
Alcohol Abuse
Interventions Drug: dutasteride + ethanol
Drug: placebo medication + ethanol
Drug: dutasteride + placebo alcohol
Drug: placebo medication + placebo alcohol
Enrollment 94
Recruitment Details Non-treatment seeking social drinkers recruited from community settings 2007-2010.
Pre-assignment Details A total of 148 subjects enrolled, 31 subjects were excluded for not meeting entrance criteria, 23 subjects withdrew before first dose of study medication. 94 subjects were randomized to one of 24 possible laboratory session sequences for exposure to each of 4 treatment conditions.
Arm/Group Title Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Hide Arm/Group Description placebo medication paired with placebo alcohol placebo medication paired with active alcohol 4 mg dutasteride paired with placebo alcohol 4 mg dutasteride paired with active alcohol
Period Title: Lab Session 1
Started 24 23 26 21
Completed 22 23 26 21
Not Completed 2 0 0 0
Reason Not Completed
Withdrawal by Subject             2             0             0             0
Period Title: Washout 1
Started 22 23 26 21
Completed 21 18 24 18
Not Completed 1 5 2 3
Reason Not Completed
Withdrawal by Subject             1             5             2             3
Period Title: Lab Session 2
Started 19 [1] 21 [1] 21 [1] 20 [1]
Completed 18 21 21 19
Not Completed 1 0 0 1
Reason Not Completed
Withdrawal by Subject             1             0             0             1
[1]
subjects cross-over to different treatment condition with each lab session in factorial design,
Period Title: Washout 2
Started 18 21 21 19
Completed 17 20 20 19
Not Completed 1 1 1 0
Reason Not Completed
Withdrawal by Subject             1             1             1             0
Period Title: Lab Session 3
Started 18 [1] 19 [1] 20 [1] 19 [1]
Completed 18 19 20 19
Not Completed 0 0 0 0
[1]
subjects cross-over to different treatment condition with each lab session in factorial design,
Period Title: Washout 3
Started 18 19 20 19
Completed 17 19 20 18
Not Completed 1 0 0 1
Reason Not Completed
Withdrawal by Subject             1             0             0             1
Period Title: Lab Session 4
Started 20 [1] 18 [1] 16 [1] 20 [1]
Completed 20 18 16 19
Not Completed 0 0 0 1
Reason Not Completed
Withdrawal by Subject             0             0             0             1
[1]
subjects cross-over to different treatment condition with each lab session in factorial design,
Arm/Group Title All Study Participants
Hide Arm/Group Description All study participants enrolled in Lab Session 1
Overall Number of Baseline Participants 94
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants
<=18 years
0
   0.0%
Between 18 and 65 years
94
 100.0%
>=65 years
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 94 participants
26.1  (6.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants
Female
0
   0.0%
Male
94
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 94 participants
94
1.Primary Outcome
Title Breath Alcohol
Hide Description Breath Alcohol level
Time Frame 40 minutes after beginning drink
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who completed all 4 arms of study (e.g. completed each combination of dutasteride or placebo paired with 0.8 gr/kg ethanol or alcohol flavor mask)less 3 subjects removed during data cleaning due to pharmacy errors (n=2) or protocol deviation (n=1)resulted in 70 subjects completing each condition for analysis.
Arm/Group Title Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Hide Arm/Group Description:
placebo medication paired with placebo alcohol
placebo medication paired with active alcohol
4 mg dutasteride paired with placebo alcohol
4 mg dutasteride paired with active alcohol
Overall Number of Participants Analyzed 70 70 70 70
Mean (Standard Error)
Unit of Measure: gr/dL
0.001  (0.0004) 0.075  (0.003) 0.001  (0.0005) 0.071  (0.003)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Medication + 0.8 gr/kg Ethanol, 4 mg Dutasteride + 0.8 mg/kg Ethanol
Comments null hypothesis - dutasteride does not affect blood alcohol following standardized dose of alcohol (0.8 gr/kg)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title BAES Sedation Response, Average of 6 Time Points
Hide Description Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all)to 10 (extremely)- for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score 0-70 with higher numbers indicating greater sedative effects of alcohol. [Martin, C. S., M. Earleywine, R. E. Musty, M. W. Perrine and R. M. Swift (1993a). Development and validation of the Biphasic Alcohol Effects Scale. Alcohol Clin Exp Res 17(1): 140-6.]
Time Frame 40, 80, 120, 160, 210 and 240 minutes after start of drinking
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who completed all 4 arms of study (e.g. completed each combination of dutasteride or placebo paired with 0.8 gr/kg ethanol or alcohol flavor mask)less 3 subjects removed during data cleaning due to pharmacy errors (n=2) or protocol deviation (n=1)resulted in 70 subjects completing each condition for analysis.
Arm/Group Title Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Hide Arm/Group Description:
placebo medication paired with placebo alcohol
placebo medication paired with active alcohol
4 mg dutasteride paired with placebo alcohol
4 mg dutasteride paired with active alcohol
Overall Number of Participants Analyzed 70 70 70 70
Mean (Standard Error)
Unit of Measure: units on a scale
0.7  (0.1) 8.9  (0.6) 1.5  (0.2) 7.4  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Medication + 0.8 gr/kg Ethanol, 4 mg Dutasteride + 0.8 mg/kg Ethanol
Comments null hypothesis: dutasteride pre-treatment does not reduce the sedative effect of alcohol
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Primary Outcome
Title BAES Stimulation Response, Average of 6 Time Points
Hide Description Biphasic Alcohol Effects Scale (BAES)Simulation items - sum of subjective responses - 0(not at all)to 10 (extremely)- for 7 stimulation related questions regarding effects of alcohol. Total BAES stimulation subscale score 0-70 with higher numbers indicating greater stimulating effects of alcohol. [Martin, C. S., M. Earleywine, R. E. Musty, M. W. Perrine and R. M. Swift (1993a). Development and validation of the Biphasic Alcohol Effects Scale. Alcohol Clin Exp Res 17(1): 140-6.]
Time Frame 40, 80, 120, 160, 210 and 240 minutes after start of drinking
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who completed all 4 arms of study (e.g. completed each combination of dutasteride or placebo paired with 0.8 gr/kg ethanol or alcohol flavor mask)less 3 subjects removed during data cleaning due to pharmacy errors (n=2) or protocol deviation (n=1)resulted in 70 subjects completing each condition for analysis.
Arm/Group Title Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Hide Arm/Group Description:
placebo medication paired with placebo alcohol
placebo medication paired with active alcohol
4 mg dutasteride paired with placebo alcohol
4 mg dutasteride paired with active alcohol
Overall Number of Participants Analyzed 70 70 70 70
Mean (Standard Error)
Unit of Measure: units on a scale
0.7  (0.1) 4.2  (0.4) 1.7  (0.3) 4.8  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Medication + 0.8 gr/kg Ethanol, 4 mg Dutasteride + 0.8 mg/kg Ethanol
Comments null hypothesis: dutasteride pre-treatment does not reduce the stimulating effect of alcohol
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
4.Secondary Outcome
Title Change in Serum 3a-androstanediol Glucuronide
Hide Description Ratio of serum 3a-androstanediol drawn prior to alcohol administration (2-4 days after medication administration) compared to the baseline level prior to medication dose. The pharmacologic effect of dutasteride was measured by assay of serum 5a-androstan-3a,17b-diol,17-glucuronide (aka 3a-androstanediol glucuronide) as a biochemical measure of 5a-reductase enzyme inhibition. 3a-androstanediol glucuronide is the primary metabolic excretion product of 3a,5a-androstane neuroactive steroids. The
Time Frame Baseline (pre medication administration) and 2-4 days post-medication (alcohol session)
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who completed all 4 arms of study (e.g. completed each combination of dutasteride or placebo paired with 0.8 gr/kg ethanol or alcohol flavor mask)less 3 subjects removed during data cleaning due to pharmacy errors (n=2) or protocol deviation (n=1)resulted in 70 subjects completing each condition for analysis.
Arm/Group Title Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Hide Arm/Group Description:
placebo medication paired with placebo alcohol
placebo medication paired with active alcohol
4 mg dutasteride paired with placebo alcohol
4 mg dutasteride paired with active alcohol
Overall Number of Participants Analyzed 70 70 70 70
Mean (Standard Error)
Unit of Measure: ratio
1.04  (0.033) 1.11  (0.03) 0.31  (0.02) 0.31  (0.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Medication + 0.8 gr/kg Ethanol, 4 mg Dutasteride + 0.8 mg/kg Ethanol
Comments null hypothesis - A single 4 mg dose of dutasteride does not reduce serum 3a-androstanediol glucuronide levels
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 2-11 days following medication administration. In person at time of alcohol laboratory session (2-4 days after medication dose)and by phone 1-day and 1-week following alcohol laboratory session.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Hide Arm/Group Description placebo medication paired with placebo alcohol placebo medication paired with active alcohol 4 mg dutasteride paired with placebo alcohol 4 mg dutasteride paired with active alcohol
All-Cause Mortality
Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/78 (0.00%)      0/81 (0.00%)      0/83 (0.00%)      0/78 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Placebo Medication + Placebo Alcohol Placebo Medication + 0.8 gr/kg Ethanol 4 mg Dutasteride + Placebo Alcohol 4 mg Dutasteride + 0.8 mg/kg Ethanol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/78 (11.54%)      8/81 (9.88%)      11/83 (13.25%)      12/78 (15.38%)    
Gastrointestinal disorders         
Nausea *  1/78 (1.28%)  1 0/81 (0.00%)  0 2/83 (2.41%)  2 2/78 (2.56%)  2
Stomach discomfort *  2/78 (2.56%)  2 2/81 (2.47%)  2 4/83 (4.82%)  5 6/78 (7.69%)  7
General disorders         
Fatigue *  2/78 (2.56%)  2 2/81 (2.47%)  2 2/83 (2.41%)  3 1/78 (1.28%)  1
Musculoskeletal and connective tissue disorders         
Musculoskeletal Pain *  1/78 (1.28%)  1 1/81 (1.23%)  1 1/83 (1.20%)  1 0/78 (0.00%)  0
Nervous system disorders         
Headace *  2/78 (2.56%)  2 3/81 (3.70%)  3 1/83 (1.20%)  1 3/78 (3.85%)  3
Reproductive system and breast disorders         
Libido, reduced *  1/78 (1.28%)  1 0/81 (0.00%)  0 1/83 (1.20%)  1 0/78 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jonathan Covault
Organization: University of Connecticut Health Center
Phone: 860-679-7560
EMail: jocovault@uchc.edu
Layout table for additonal information
Responsible Party: Jonathan Covault, UConn Health
ClinicalTrials.gov Identifier: NCT00734656     History of Changes
Other Study ID Numbers: 06-218S-2
619 ( Other Grant/Funding Number: GCRC )
5R01AA015606-02 ( U.S. NIH Grant/Contract )
First Submitted: July 31, 2008
First Posted: August 14, 2008
Results First Submitted: October 27, 2011
Results First Posted: March 27, 2012
Last Update Posted: March 28, 2012