Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
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

Tracking Information
First Submitted Date  ICMJE July 31, 2008
First Posted Date  ICMJE August 14, 2008
Results First Submitted Date  ICMJE October 27, 2011
Results First Posted Date  ICMJE March 27, 2012
Last Update Posted Date March 28, 2012
Study Start Date  ICMJE March 2007
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2012)
  • 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.]
Original Primary Outcome Measures  ICMJE
 (submitted: August 13, 2008)
Subjective measure of alcohol effects, static ataxia, working memory and neuroactive steroid levels as a function of alcohol vs. placebo and dutasteride vs. placebo and stratified by GABRG1-GABRA2 genotype. [ Time Frame: Semi-annually ]
Change History Complete list of historical versions of study NCT00734656 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2012)
Change in Serum 3a-androstanediol Glucuronide [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacogenetics of Alcohol: Treatment Implications
Official Title  ICMJE Subjective and Physiological Effects of Alcohol: Role of Genetic Variation and Adrenal Hormones
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Condition  ICMJE
  • Alcohol Related Disorders
  • Alcoholism
  • Alcohol Abuse
Intervention  ICMJE
  • Drug: dutasteride + ethanol
    4 mg dutasteride administered 2-4 days prior to ingestion of 0.8 mg/kg ethanol divided between three drinks consumed over 36 minutes
    Other Name: Avodart
  • Drug: placebo medication + ethanol
    placebo medication administered 2-4 days prior to ingestion of 0.8 gr/kg ethanol divided between three drinks consumed over 36 minutes
  • Drug: dutasteride + placebo alcohol
    4 mg dutasteride administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes
    Other Name: Avodart
  • Drug: placebo medication + placebo alcohol
    placebo medication administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes
Study Arms  ICMJE
  • Placebo Comparator: Placebo medication + placebo alcohol
    Intervention: Drug: placebo medication + placebo alcohol
  • Experimental: Placebo Medication + 0.8 gr/kg Ethanol
    Intervention: Drug: placebo medication + ethanol
  • Experimental: 4 mg Dutasteride + Placebo Alcohol
    Intervention: Drug: dutasteride + placebo alcohol
  • Experimental: 4 mg Dutasteride + 0.8 gr/kg Ethanol
    Intervention: Drug: dutasteride + ethanol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 21, 2012)
94
Original Estimated Enrollment  ICMJE
 (submitted: August 13, 2008)
140
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 21 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00734656
Other Study ID Numbers  ICMJE 06-218S-2
619 ( Other Grant/Funding Number: GCRC )
5R01AA015606-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jonathan Covault, UConn Health
Study Sponsor  ICMJE UConn Health
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators  ICMJE
Principal Investigator: Jonathan Covault, MD, PhD UConn Health
PRS Account UConn Health
Verification Date March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP