Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Yale University
Sponsor:
Collaborator:
VA Connecticut Healthcare System
Information provided by (Responsible Party):
Ismene Petrakis, Yale University
ClinicalTrials.gov Identifier:
NCT00612352
First received: December 27, 2007
Last updated: February 14, 2013
Last verified: February 2013

December 27, 2007
February 14, 2013
March 2001
July 2013   (final data collection date for primary outcome measure)
Biphasic Alcohol Affects Scale (BAES), Positive and Negative Symptom Scale (PANSS), visual analog scales of mood states (i.e. anxiety) and the Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: Baseline, +20, +40, +80, +110, +170, +230 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00612352 on ClinicalTrials.gov Archive Site
visual analog scales for high, similarity to ethanol, Mini Mental Status Examination (MMSE) [ Time Frame: Baseline, +20, +40, +80, +110, +170, +230 ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism
Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism

The proposed study is the first to explore the contribution of brain glutamate systems, a major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study may lead to an enhanced understanding of the underlying neurobiological mechanism in high risk individuals that may lead to the transition from moderate to excessive use of alcohol.

Males and females with a paternal family history of alcoholism have a high risk for developing alcoholism. These individuals have been shown to have decreased dysphoric responses to alcohol self-administration that may promote the excessive use of alcohol. Ethanol has been shown to be an antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. We have recently shown that sober alcoholics have decreased dysphoric response to the NMDA antagonist, ketamine. We propose to test the hypothesis that this characteristic exists as a vulnerability factor in those individuals susceptible to develop alcoholism. Specifically, the objective is to determine whether individuals with a family history positive (FHP) for alcoholism will experience less dysphoric, anxiogenic, and psychotogenic effects to alcohol infusion when compared to family history negative (FHN) control subjects.

Male and female subjects, FHP (biological father and one other first degree relative) between the ages of 21-30, and matched controls (FHN) will complete 3 test days in a randomized balanced order under double-blind conditions. Test days will involve administration of placebo or one of two ethanol doses (target BrAc=40mg%, or target BrAc=100mg%) intravenously for 20 minutes, until the target BrAc is achieved. Once BrAc is achieved (40mg% or 100mg%) it will be maintained using a clamp procedure for over 60 minutes. Outcome measures include the Positive and Negative Symptom Scale, visual analog scales of mood state, (i.e. anxiety) and the Clinician-Administered Dissociative States Scale (CADSS) to measure perceptual responses to alcohol. Secondary measures include visual analog scales for high, similarity to ethanol, Mini Mental Status Examination (MMSE), Placement of electrodes, Biphasic Alcohol Effects Scale, Hopkins Verbal Learning, and number of drinks scale, aspects of craving for alcohol and tests of cognitive impairment.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Alcoholism
Drug: Ethanol High Dose and Ethanol Low Dose
Test days will involve administration of placebo, ethanol high dose (BrAc=100mg%) or ethanol low dose (BrAc=40mg%)intravenously for approximately 20 minutes, until the target BrAc is achieved. Once BrAc is achieved (40mg% or 100mg%) it will be maintained using a clamp procedure for 60 minutes.
Other Name: Alcohol intravenous
  • Active Comparator: Ethanol High Dose
    Ethanol administered through an IV to 0.1 and clamped for 1 hour.
    Intervention: Drug: Ethanol High Dose and Ethanol Low Dose
  • Active Comparator: Ethanol Low Dose
    Ethanol administered through an IV to 0.04 and clamped for 1 hour.
    Intervention: Drug: Ethanol High Dose and Ethanol Low Dose
  • Placebo Comparator: Placebo
    Placebo administered through an IV and clamped for 1 hour.
    Intervention: Drug: Ethanol High Dose and Ethanol Low Dose

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
September 2013
July 2013   (final data collection date for primary outcome measure)

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, EKG, Screening laboratories absence of current and/or past substance abuse on the basis of history and urine toxicology and breath alcohol levels at screening and on each test day.

For Family History Positive (FHP) Subjects: 1) Biological father and another first or second-degree biological relative with history of alcoholism by FHAM-Family History Assessment Module developed by COGA.

Exclusion Criteria:

  1. DSM-IV psychiatric and substance abuse (excluding alcohol abuse) diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (Structured Clinical Interview for DSM-IV Axis I Disorders: SCID)
  2. Subjects who meet criteria for alcohol abuse and express an interest in stopping alcohol use and/or express an interest in treatment or are currently enrolled in treatment for alcoholism, or have sought treatment in the last 6 months.
  3. history of counseling or psychotherapy; except family therapy centered around another family member
  4. extended unwillingness to remain alcohol-free for 48 hours prior to test days;
  5. for women: positive pregnancy test at screening or intention to engage in unprotected sex during the study
  6. alcohol naïve
  7. Adoptee and no contact with family members.
Both
21 Years to 30 Years
Yes
United States
 
NCT00612352
0304025194, VA Alcohol Research Center
Yes
Ismene Petrakis, Yale University
Yale University
VA Connecticut Healthcare System
Principal Investigator: Ismene L Petrakis, MD Yale University
Yale University
February 2013

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