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
  Purpose

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.


Condition Intervention
Alcoholism
Drug: Ethanol High Dose and Ethanol Low Dose

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Official Title: Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 200
Study Start Date: March 2001
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ethanol High Dose
Ethanol administered through an IV to 0.1 and clamped for 1 hour.
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 Low Dose
Ethanol administered through an IV to 0.04 and clamped for 1 hour.
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
Placebo Comparator: Placebo
Placebo administered through an IV and clamped for 1 hour.
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

Detailed Description:

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.

  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, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612352

Locations
United States, Connecticut
VA Connecticut Healthcare System Recruiting
West Haven, Connecticut, United States, 06516
Contact: Diana Limoncelli, BA    203-397-7684 ext 5217    diana.limoncelli@yale.edu   
Sponsors and Collaborators
Yale University
VA Connecticut Healthcare System
Investigators
Principal Investigator: Ismene L Petrakis, MD Yale University
  More Information

Publications:
Responsible Party: Ismene Petrakis, Professor of Psychiatry, Yale University
ClinicalTrials.gov Identifier: NCT00612352     History of Changes
Other Study ID Numbers: 0304025194, VA Alcohol Research Center
Study First Received: December 27, 2007
Last Updated: February 14, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ethanol
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 01, 2014