Trial Outcomes & Findings for Pharmacogenetics of Alcohol: Treatment Implications (NCT NCT00734656)

NCT ID: NCT00734656

Last Updated: 2012-03-28

Results Overview

Breath Alcohol level

Recruitment status

COMPLETED

Study phase

Target enrollment

94 participants

Primary outcome timeframe

40 minutes after beginning drink

Results posted on

2012-03-28

Participant Flow

Non-treatment seeking social drinkers recruited from community settings 2007-2010.

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.

Participant milestones

Participant milestones
Measure	Placebo Medication + Placebo Alcohol placebo medication paired with placebo alcohol	Placebo Medication + 0.8 gr/kg Ethanol placebo medication paired with active alcohol	4 mg Dutasteride + Placebo Alcohol 4 mg dutasteride paired with placebo alcohol	4 mg Dutasteride + 0.8 mg/kg Ethanol 4 mg dutasteride paired with active alcohol
Lab Session 1 STARTED	24	23	26	21
Lab Session 1 COMPLETED	22	23	26	21
Lab Session 1 NOT COMPLETED	2	0	0	0
Washout 1 STARTED	22	23	26	21
Washout 1 COMPLETED	21	18	24	18
Washout 1 NOT COMPLETED	1	5	2	3
Lab Session 2 STARTED	19	21	21	20
Lab Session 2 COMPLETED	18	21	21	19
Lab Session 2 NOT COMPLETED	1	0	0	1
Washout 2 STARTED	18	21	21	19
Washout 2 COMPLETED	17	20	20	19
Washout 2 NOT COMPLETED	1	1	1	0
Lab Session 3 STARTED	18	19	20	19
Lab Session 3 COMPLETED	18	19	20	19
Lab Session 3 NOT COMPLETED	0	0	0	0
Washout 3 STARTED	18	19	20	19
Washout 3 COMPLETED	17	19	20	18
Washout 3 NOT COMPLETED	1	0	0	1
Lab Session 4 STARTED	20	18	16	20
Lab Session 4 COMPLETED	20	18	16	19
Lab Session 4 NOT COMPLETED	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Medication + Placebo Alcohol placebo medication paired with placebo alcohol	Placebo Medication + 0.8 gr/kg Ethanol placebo medication paired with active alcohol	4 mg Dutasteride + Placebo Alcohol 4 mg dutasteride paired with placebo alcohol	4 mg Dutasteride + 0.8 mg/kg Ethanol 4 mg dutasteride paired with active alcohol
Lab Session 1 Withdrawal by Subject	2	0	0	0
Washout 1 Withdrawal by Subject	1	5	2	3
Lab Session 2 Withdrawal by Subject	1	0	0	1
Washout 2 Withdrawal by Subject	1	1	1	0
Washout 3 Withdrawal by Subject	1	0	0	1
Lab Session 4 Withdrawal by Subject	0	0	0	1

Baseline Characteristics

Pharmacogenetics of Alcohol: Treatment Implications

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=94 Participants All study participants enrolled in Lab Session 1
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	94 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	26.1 years STANDARD_DEVIATION 6.5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	94 Participants n=5 Participants
Region of Enrollment United States	94 participants n=5 Participants

PRIMARY outcome

Timeframe: 40 minutes after beginning drink

Population: 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.

Breath Alcohol level

Outcome measures

Outcome measures
Measure	Placebo Medication + Placebo Alcohol n=70 Participants placebo medication paired with placebo alcohol	Placebo Medication + 0.8 gr/kg Ethanol n=70 Participants placebo medication paired with active alcohol	4 mg Dutasteride + Placebo Alcohol n=70 Participants 4 mg dutasteride paired with placebo alcohol	4 mg Dutasteride + 0.8 mg/kg Ethanol n=70 Participants 4 mg dutasteride paired with active alcohol
Breath Alcohol	0.001 gr/dL Standard Error 0.0004	0.075 gr/dL Standard Error 0.003	0.001 gr/dL Standard Error 0.0005	0.071 gr/dL Standard Error 0.003

PRIMARY outcome

Timeframe: 40, 80, 120, 160, 210 and 240 minutes after start of drinking

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. \[Martin, C. S., M. Earleywine, R. E. Musty, M. W. Perrine and R. M. Swift (1993a). Development and validation of the Biphasic Alcohol Effects Scale. Alcohol Clin Exp Res 17(1): 140-6.\]

Outcome measures

Outcome measures
Measure	Placebo Medication + Placebo Alcohol n=70 Participants placebo medication paired with placebo alcohol	Placebo Medication + 0.8 gr/kg Ethanol n=70 Participants placebo medication paired with active alcohol	4 mg Dutasteride + Placebo Alcohol n=70 Participants 4 mg dutasteride paired with placebo alcohol	4 mg Dutasteride + 0.8 mg/kg Ethanol n=70 Participants 4 mg dutasteride paired with active alcohol
BAES Sedation Response, Average of 6 Time Points	0.7 units on a scale Standard Error 0.1	8.9 units on a scale Standard Error 0.6	1.5 units on a scale Standard Error 0.2	7.4 units on a scale Standard Error 0.5

PRIMARY outcome

Timeframe: 40, 80, 120, 160, 210 and 240 minutes after start of drinking

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. \[Martin, C. S., M. Earleywine, R. E. Musty, M. W. Perrine and R. M. Swift (1993a). Development and validation of the Biphasic Alcohol Effects Scale. Alcohol Clin Exp Res 17(1): 140-6.\]

Outcome measures

Outcome measures
Measure	Placebo Medication + Placebo Alcohol n=70 Participants placebo medication paired with placebo alcohol	Placebo Medication + 0.8 gr/kg Ethanol n=70 Participants placebo medication paired with active alcohol	4 mg Dutasteride + Placebo Alcohol n=70 Participants 4 mg dutasteride paired with placebo alcohol	4 mg Dutasteride + 0.8 mg/kg Ethanol n=70 Participants 4 mg dutasteride paired with active alcohol
BAES Stimulation Response, Average of 6 Time Points	0.7 units on a scale Standard Error 0.1	4.2 units on a scale Standard Error 0.4	1.7 units on a scale Standard Error 0.3	4.8 units on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: Baseline (pre medication administration) and 2-4 days post-medication (alcohol session)

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

Outcome measures

Outcome measures
Measure	Placebo Medication + Placebo Alcohol n=70 Participants placebo medication paired with placebo alcohol	Placebo Medication + 0.8 gr/kg Ethanol n=70 Participants placebo medication paired with active alcohol	4 mg Dutasteride + Placebo Alcohol n=70 Participants 4 mg dutasteride paired with placebo alcohol	4 mg Dutasteride + 0.8 mg/kg Ethanol n=70 Participants 4 mg dutasteride paired with active alcohol
Change in Serum 3a-androstanediol Glucuronide	1.04 ratio Standard Error 0.033	1.11 ratio Standard Error 0.03	0.31 ratio Standard Error 0.02	0.31 ratio Standard Error 0.02

Adverse Events

Placebo Medication + Placebo Alcohol

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo Medication + 0.8 gr/kg Ethanol

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

4 mg Dutasteride + Placebo Alcohol

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

4 mg Dutasteride + 0.8 mg/kg Ethanol

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo Medication + Placebo Alcohol n=78 participants at risk placebo medication paired with placebo alcohol	Placebo Medication + 0.8 gr/kg Ethanol n=81 participants at risk placebo medication paired with active alcohol	4 mg Dutasteride + Placebo Alcohol n=83 participants at risk 4 mg dutasteride paired with placebo alcohol	4 mg Dutasteride + 0.8 mg/kg Ethanol n=78 participants at risk 4 mg dutasteride paired with active alcohol
General disorders Fatigue	2.6% 2/78 • Number of events 2 • 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.	2.5% 2/81 • Number of events 2 • 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.	2.4% 2/83 • Number of events 3 • 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.	1.3% 1/78 • Number of events 1 • 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.
Nervous system disorders Headace	2.6% 2/78 • Number of events 2 • 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.	3.7% 3/81 • Number of events 3 • 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.	1.2% 1/83 • Number of events 1 • 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.	3.8% 3/78 • Number of events 3 • 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.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	1.3% 1/78 • Number of events 1 • 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.	1.2% 1/81 • Number of events 1 • 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.	1.2% 1/83 • Number of events 1 • 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.	0.00% 0/78 • 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.
Gastrointestinal disorders Nausea	1.3% 1/78 • Number of events 1 • 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.	0.00% 0/81 • 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.	2.4% 2/83 • Number of events 2 • 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.	2.6% 2/78 • Number of events 2 • 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.
Reproductive system and breast disorders Libido, reduced	1.3% 1/78 • Number of events 1 • 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.	0.00% 0/81 • 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.	1.2% 1/83 • Number of events 1 • 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.	0.00% 0/78 • 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.
Gastrointestinal disorders Stomach discomfort	2.6% 2/78 • Number of events 2 • 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.	2.5% 2/81 • Number of events 2 • 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.	4.8% 4/83 • Number of events 5 • 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.	7.7% 6/78 • Number of events 7 • 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.

Additional Information

Jonathan Covault

University of Connecticut Health Center

Phone: 860-679-7560

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place