GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ismene Petrakis, Yale University
ClinicalTrials.gov Identifier:
NCT00611767
First received: December 27, 2007
Last updated: November 2, 2012
Last verified: January 2008
  Purpose

This Project will explore the hypothesis that individuals with a family history positive for alcohol dependence (without any current Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABAA receptor agonist barbiturate (thiopental) compared to family history negative age-matched subjects. Further, variation in genes involved in brain GABA function may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.


Condition Intervention
Alcoholism
Drug: Thiopental
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Biphasic Alcohol Effects Scale, confirmed with other measures such as the Visual Analog Scales [ Time Frame: Baseline, +10, +20, +80, +110, +170, +230 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • potential response P300 measurements, grooved pegboard test [ Time Frame: Baseline and during infusion ] [ Designated as safety issue: Yes ]

Enrollment: 2
Study Start Date: November 2005
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Thiopental
thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).
Drug: Thiopental
A 2-day test design involving 2 conditions: saline or thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).
Placebo Comparator: Placebo
saline (60 minute infusion).
Drug: Placebo
Placebo

Detailed Description:

This project will explore the hypothesis that individuals with a family history positive for alcohol dependence (FHP) (without any current DSM-IV Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABA-A receptor agonist barbiturate (thiopental) compared to family history negative (FHN) age-matched subjects. Further, the effect of variations in genes important in regulating brain GABA function may alter a component of the discriminative stimulus effects of ethanol. FHP individuals are defined as individuals with at least one first-degree relative and another first- or second-degree relatives. Preliminary results suggest that FHP individuals showed an attenuated response to thiopental as measured by the descending limb of the BAES during thiopental infusion relative to the FHN group. Further, preliminary results suggest that variation in genes involved in brain GABA function, glutamate decarboxylase-65 (GAD65), may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.

We plan to recruit 2 groups of healthy subjects between the ages of 21-30, one with a family history of alcoholism (family history positive=FHP) and a sex-matched control group without a family history of alcoholism (family history negative=FHN), to undergo two test days scheduled 3 days apart, in a randomized double-blind fashion. Test days will involve a 60-minute intravenous infusion of each of 2 conditions: saline or thiopental, in a randomized order under double-blind conditions. Behavioral ratings include the Biphasic Alcohol Effects Scale (BAES) and Visual Analog Scales (VAS). Exploratory measures include event-related potential recordings (ERP) and measures of eye-to-hand coordination. Blood will be collected for Deoxyribonucleic acid (DNA) extraction and genotyping.

  Eligibility

Ages Eligible for Study:   21 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male and female between the ages of 21 and 30 years
  2. medically and neurologically healthy on the basis of history, physical examination, Electrocardiogram (EKG), screening laboratories
  3. absence of any evidence of substance abuse (with the exception of nicotine dependence) on the basis of history and drug and ethanol-free at the time of testing based on urine toxicology and breath alcohol levels at screening and on each test day.

Exclusion Criteria:

  1. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) Axis I psychiatric and substance abuse or dependence diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (SCID)
  2. unwillingness to remain alcohol-free for three days prior to each test day;
  3. for women, positive pregnancy test at screening or intention to engage in unprotected sex during the study and
  4. alcohol naive. For Family History Positive Subjects: 1) Biological father and another first or second-degree biological relative with history of alcoholism by Family History Assessment Module (FHAM) developed by COGA.

For Family History Negative Subjects: NO family history of alcoholism in any first or second-degree relatives. Subjects must reliably report on three first-degree relatives.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00611767

Locations
United States, Connecticut
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Ismene L Petrakis, MD Yale University
  More Information

No publications provided

Responsible Party: Ismene Petrakis, Professor of Psychiatry, Yale University
ClinicalTrials.gov Identifier: NCT00611767     History of Changes
Other Study ID Numbers: 0510000664, VA Merit Grant
Study First Received: December 27, 2007
Last Updated: November 2, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Thiopental
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014