Alcohol Related DisordersNCT00734656
Pharmacogenetics of Alcohol: Treatment Implications
A study testing dutasteride + ethanol in people with Alcohol Related Disorders and Alcoholism, run by UConn Health at 1 site in United States.
Trial summary
This study will explore the hypothesis that effects of alcohol are in part mediated by increased production of neuroactive steroids, which interact with GABAA-receptors. We propose to study non-dependent drinkers using a 4-session within-subjects design in which alcohol / placebo is paired with dutasteride / placebo… Read more about this study
- Who is it for?
- Ages 21 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Alcohol Related Disorders, Alcoholism, Alcohol Abuse
- What is being tested?
- dutasteride + ethanol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Jul 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Main Study: Subjects will be healthy volunteers with or without parental history of alcoholism who are 21-45 years old and who have a BMI >18.5 and <32.5. Drinking history: All subjects must report at least one occasion in the prior month of drinking at least 3 drinks on a single day; additionally, LD subjects will be selected if they drink 1-3 drinks, 1-3 times per week (up to 5 drinks per week on average), with no more than one occasion in the past 2 months on which they drank >4 drinks. HD subjects will be selected if they report drinking at least 10 drinks per week, with at least one episode per week of heavy drinking.
Who cannot join
- Main Study: Subjects cannot have a current or past DSM-IV diagnosis of alcohol or drug dependence, current or past 24-months diagnosis of alcohol or drug abuse or another major psychiatric disorder, neurological illness, have had a hypersensitivity reaction to dutasteride, evidence of liver dysfunction, currently be using benzodiazepines, other psychotropic medications or medications that are known to influence steroid hormone levels or metabolism or modify the effects of alcohol. Nicotine-dependent subjects will be excluded to avoid the confounding effects of nicotine withdrawal during day-long laboratory sessions. Women are not allowed to participate. Subjects anticipating moving from the area during the period of their planned study participation will be excluded from study entry.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Connecticut Health Center
Farmington, Connecticut, 06030
About this study
Official title: Subjective and Physiological Effects of Alcohol: Role of Genetic Variation and Adrenal Hormones
This study will explore the hypothesis that effects of alcohol are in part mediated by increased production of neuroactive steroids, which interact with GABAA-receptors. We propose to study non-dependent drinkers using a 4-session within-subjects design in which alcohol / placebo is paired with dutasteride / placebo pretreatment. Dutasteride is a 5-alpha steroid reductase (5AR) inhibitor that limits the production of dihydrotestosterone and the 5a-reduced neuroactive steroids allopregnanolone, pregnanolone and 3a,5a-androstanediol.
Read the detailed description
Alcohol has multiple pharmacological effects, though which of these effects relate to the risk of alcohol dependence is not clear. Animal studies indicate that the neuroactive steroid allopregnanolone is an alcohol-modulated endogenous agonist at GABAA receptors and that genetic variation in steroid 5a-reductase type I gene which generates neuroactive steroids, may moderate alcohol effects. To better define the role of neuroactive steroids we will conduct a laboratory study of non-alcohol dependent drinkers using a 4-session design in which alcohol/placebo beverage is paired with dutasteride/placebo pretreatment. Dutasteride, an inhibitor of both type I and type II 5a-reductase enzymes, blocks the production of 5a-reduced neuroactive steroids. This study will extend our preliminary findings with finasteride by including a) a placebo control for alcohol, b) a more specific inhibitor of both 5a-reductase isoenzymes, c) a larger group of subjects (including both light and heavy drinkers).
- Conditions
- Alcohol Related Disorders, Alcoholism, Alcohol Abuse
- Being tested
- dutasteride + ethanol, placebo medication + ethanol, dutasteride + placebo alcohol, placebo medication + placebo alcohol
- Keywords
- steroid 5Alpha Reductase, dutasteride, neuroactive steroid
- Medical subject headings
- Alcohol-Related Disorders, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dutasteride + ethanolDrug
Also called Avodart
4 mg dutasteride administered 2-4 days prior to ingestion of 0.8 mg/kg ethanol divided between three drinks consumed over 36 minutes
placebo medication + ethanolDrug
placebo medication administered 2-4 days prior to ingestion of 0.8 gr/kg ethanol divided between three drinks consumed over 36 minutes
dutasteride + placebo alcoholDrug
Also called Avodart
4 mg dutasteride administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes
placebo medication + placebo alcoholDrug
placebo medication administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes
| Study group | Role | What they receive |
|---|---|---|
| Placebo medication + placebo alcohol | Placebo comparator | Not described Receives: Drug: placebo medication + placebo alcohol |
| Placebo Medication + 0.8 gr/kg Ethanol | Experimental | Not described Receives: Drug: placebo medication + ethanol |
| 4 mg Dutasteride + Placebo Alcohol | Experimental | Not described Receives: Drug: dutasteride + placebo alcohol |
| 4 mg Dutasteride + 0.8 gr/kg Ethanol | Experimental | Not described Receives: Drug: dutasteride + ethanol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Breath Alcohol
Breath Alcohol level
Measured: 40 minutes after beginning drink
BAES Sedation Response, Average of 6 Time Points
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.]
Measured: 40, 80, 120, 160, 210 and 240 minutes after start of drinking
BAES Stimulation Response, Average of 6 Time Points
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.]
Measured: 40, 80, 120, 160, 210 and 240 minutes after start of drinking
Secondary outcomes (1)
Change in Serum 3a-androstanediol Glucuronide
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
Measured: Baseline (pre medication administration) and 2-4 days post-medication (alcohol session)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startMar 2007
- Primary completionOct 2010
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcohol Related DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Jonathan Covault, UConn Health
- Investigators
- Jonathan Covault, MD, PhD, Principal investigator, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734656
- Sponsor's protocol ID
- 06-218S-2
- Other IDs
- 619, 5R01AA015606-02
- Status last verified
- Mar 2012
- First submitted
- 31 Jul 2008
- Last updated
- 28 Mar 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subjective and Physiological Effects of Alcohol: Role of Genetic Variation and Adrenal Hormones
- ClinicalTrials.gov ID
- NCT00734656
- Acronym / sponsor ID
- 06-218S-2
- Conditions
- Alcohol Related Disorders, Alcoholism, Alcohol Abuse
- Keywords
- steroid 5Alpha Reductase, dutasteride, neuroactive steroid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- Mar 2007
- Primary completion
- Oct 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Posted 27 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will explore the hypothesis that effects of alcohol are in part mediated by increased production of neuroactive steroids, which interact with GABAA-receptors. We propose to study non-dependent drinkers using a 4-session within-subjects design in which alcohol / placebo is paired with dutasteride / placebo pretreatment. Dutasteride is a 5-alpha steroid reductase (5AR) inhibitor that limits the production of dihydrotestosterone and the 5a-reduced neuroactive steroids allopregnanolone, pregnanolone and 3a,5a-androstanediol.
Detailed description
Alcohol has multiple pharmacological effects, though which of these effects relate to the risk of alcohol dependence is not clear. Animal studies indicate that the neuroactive steroid allopregnanolone is an alcohol-modulated endogenous agonist at GABAA receptors and that genetic variation in steroid 5a-reductase type I gene which generates neuroactive steroids, may moderate alcohol effects. To better define the role of neuroactive steroids we will conduct a laboratory study of non-alcohol dependent drinkers using a 4-session design in which alcohol/placebo beverage is paired with dutasteride/placebo pretreatment. Dutasteride, an inhibitor of both type I and type II 5a-reductase enzymes, blocks the production of 5a-reduced neuroactive steroids. This study will extend our preliminary findings with finasteride by including a) a placebo control for alcohol, b) a more specific inhibitor of both 5a-reductase isoenzymes, c) a larger group of subjects (including both light and heavy drinkers).
Study design
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo medication + placebo alcohol | Placebo comparator | Drug: placebo medication + placebo alcohol |
| Placebo Medication + 0.8 gr/kg Ethanol | Experimental | Drug: placebo medication + ethanol |
| 4 mg Dutasteride + Placebo Alcohol | Experimental | Drug: dutasteride + placebo alcohol |
| 4 mg Dutasteride + 0.8 gr/kg Ethanol | Experimental | Drug: dutasteride + ethanol |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Main Study: Subjects will be healthy volunteers with or without parental history of alcoholism who are 21-45 years old and who have a BMI >18.5 and <32.5. Drinking history: All subjects must report at least one occasion in the prior month of drinking at least 3 drinks on a single day; additionally, LD subjects will be selected if they drink 1-3 drinks, 1-3 times per week (up to 5 drinks per week on average), with no more than one occasion in the past 2 months on which they drank >4 drinks. HD subjects will be selected if they report drinking at least 10 drinks per week, with at least one episode per week of heavy drinking.
Key exclusion criteria (1 listed)
- Main Study: Subjects cannot have a current or past DSM-IV diagnosis of alcohol or drug dependence, current or past 24-months diagnosis of alcohol or drug abuse or another major psychiatric disorder, neurological illness, have had a hypersensitivity reaction to dutasteride, evidence of liver dysfunction, currently be using benzodiazepines, other psychotropic medications or medications that are known to influence steroid hormone levels or metabolism or modify the effects of alcohol. Nicotine-dependent subjects will be excluded to avoid the confounding effects of nicotine withdrawal during day-long laboratory sessions. Women are not allowed to participate. Subjects anticipating moving from the area during the period of their planned study participation will be excluded from study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dutasteride + ethanolAlso: Avodart4 mg dutasteride administered 2-4 days prior to ingestion of 0.8 mg/kg ethanol divided between three drinks consumed over 36 minutes | Drug | 4 mg Dutasteride + 0.8 gr/kg Ethanol |
| placebo medication + ethanolplacebo medication administered 2-4 days prior to ingestion of 0.8 gr/kg ethanol divided between three drinks consumed over 36 minutes | Drug | Placebo Medication + 0.8 gr/kg Ethanol |
| dutasteride + placebo alcoholAlso: Avodart4 mg dutasteride administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes | Drug | 4 mg Dutasteride + Placebo Alcohol |
| placebo medication + placebo alcoholplacebo medication administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes | Drug | Placebo medication + placebo alcohol |
Primary outcome
Breath Alcohol
Time frame: 40 minutes after beginning drink
Breath Alcohol level
BAES Sedation Response, Average of 6 Time Points
Time frame: 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.]
BAES Stimulation Response, Average of 6 Time Points
Time frame: 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.]
1 secondary outcome
Change in Serum 3a-androstanediol Glucuronide
Time frame: Baseline (pre medication administration) and 2-4 days post-medication (alcohol session)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Covault, MD, PhD principal investigator
UConn Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing dutasteride + ethanol in people with Alcohol Related Disorders and Alcoholism, run by UConn Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Breath Alcohol (time frame: 40 minutes after beginning drink). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2012.