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

This study has been completed.
Sponsor:
Collaborators:
VA Connecticut Healthcare System
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00612352
First received: December 27, 2007
Last updated: January 3, 2017
Last verified: January 2017
  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, Ethanol Low Dose, and Placebo

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, 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:
  • Number of Drinks Felt Consumed at Baseline [ Time Frame: Baseline ]
    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  • Number of Drinks Felt Consumed at 10 Minutes [ Time Frame: 10 minutes ]
    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  • Number of Drinks Felt Consumed at 30 Minutes [ Time Frame: 30 minutes ]
    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  • Number of Drinks Felt Consumed at 110 Minutes [ Time Frame: 110 minutes ]
    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  • Number of Drinks Felt Consumed at 140 Minutes [ Time Frame: 140 minutes ]
    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  • Number of Drinks Felt Consumed at 170 Minutes [ Time Frame: 170 minutes ]
    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  • Number of Drinks Felt Consumed at 230 Minutes [ Time Frame: 230 minutes ]
    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  • Visual Analog Scale of Similarity to Alcohol - Baseline [ Time Frame: Baseline ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol

  • Visual Analog Scale of Similarity to Alcohol -10 Minutes [ Time Frame: 10 minutes ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol

  • Visual Analog Scale of Similarity to Alcohol - 30 Minutes [ Time Frame: 30 minutes ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol

  • Visual Analog Scale of Similarity to Alcohol - 60 Minutes [ Time Frame: 60 minutes ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol

  • Visual Analog Scale of Similarity to Alcohol - 110 Minutes [ Time Frame: 110 minutes ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol

  • Visual Analog Scale of Similarity to Alcohol - 140 Minutes [ Time Frame: 140 minutes ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol

  • Visual Analog Scale of Similarity to Alcohol - 170 Minutes [ Time Frame: 170 minutes ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol

  • Visual Analog Scale of Similarity to Alcohol - 230 Minutes [ Time Frame: 230 minutes ]
    Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol


Secondary Outcome Measures:
  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline [ Time Frame: Baseline ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 10 Minutes [ Time Frame: 10 minutes ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 30 Minutes [ Time Frame: 30 minutes ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 60 Minutes [ Time Frame: 60 minutes ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes [ Time Frame: 110 minutes ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 140 Minutes [ Time Frame: 140 minutes ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes [ Time Frame: 170 minutes ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes [ Time Frame: 230 minutes ]
    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline [ Time Frame: Baseline ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 10 Minutes [ Time Frame: 10 minutes ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 30 Minutes [ Time Frame: 30 minutes ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 60 Minutes [ Time Frame: 60 minutes ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 110 Minutes [ Time Frame: 110 minutes ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 140 Minutes [ Time Frame: 140 minutes ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes [ Time Frame: 170 minutes ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 240 Minutes [ Time Frame: 240 minutes ]
    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  • Visual Analog Scale (VAS) HIGH - Baseline [ Time Frame: Baseline ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) HIGH - 10 Minutes [ Time Frame: 10 minutes ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) HIGH - 30 Minutes [ Time Frame: 30 minutes ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) HIGH - 60 Minutes [ Time Frame: 60 minutes ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) HIGH - 110 Minutes [ Time Frame: 110 minutes ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) HIGH - 140 Minutes [ Time Frame: 140 minutes ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) HIGH - 170 Minutes [ Time Frame: 170 minutes ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) HIGH - 240 Minutes [ Time Frame: 240 minutes ]
    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  • Visual Analog Scale (VAS) Drowsy - Baseline [ Time Frame: Baseline ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Visual Analog Scale (VAS) Drowsy - 10 Minutes [ Time Frame: 10 minutes ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Visual Analog Scale (VAS) Drowsy - 30 Minutes [ Time Frame: 30 minutes ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Visual Analog Scale (VAS) Drowsy - 60 Minutes [ Time Frame: 60 minutes ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Visual Analog Scale (VAS) Drowsy - 110 Minutes [ Time Frame: 110 minutes ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Visual Analog Scale (VAS) Drowsy - 140 Minutes [ Time Frame: 140 minutes ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Visual Analog Scale (VAS) Drowsy - 170 Minutes [ Time Frame: 170 minutes ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Visual Analog Scale (VAS) Drowsy - 230 Minutes [ Time Frame: 230 minutes ]
    visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

  • Hopkins Verbal Learning Task - Immediate Recall - Trial 1 [ Time Frame: 30 minutes - Trial 1 ]
    Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)

  • Hopkins Verbal Learning Task - Immediate Recall - Trial 2 [ Time Frame: 30 minutes - Trial 2 ]
    Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)

  • Hopkins Verbal Learning Task - Immediate Recall - Trial 3 [ Time Frame: 30 minutes - Trial 3 ]
    Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)

  • Hopkins Verbal Learning Task - Delay Recall [ Time Frame: 60 minutes ]
    Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Delay Recall: 30 minutes after Trials 1-3 were given) (0 no words recalled - 12 all words recalled)

  • Pegboard Task - Baseline (Dominant Hand) [ Time Frame: Baseline ]
    The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds

  • Pegboard Task - Baseline (Dominant Hand) [ Time Frame: 30 minutes ]
    The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.

  • Pegboard Task - Baseline (Non-Dominant Hand) [ Time Frame: Baseline ]
    The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.

  • Pegboard Task - Baseline (Non-Dominant Hand) [ Time Frame: 30 minutes ]
    The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.


Enrollment: 180
Study Start Date: March 2001
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Family HIstory Positive
Subjects with a positive family history of alcoholism.
Drug: Ethanol High Dose, Ethanol Low Dose, and Placebo
Three 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: intravenous
Active Comparator: Family History Negative
Subjects with a negative family history of alcoholism.
Drug: Ethanol High Dose, Ethanol Low Dose, and Placebo
Three 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: 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   (Adult)
Sexes Eligible for Study:   All
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 Family History Assessment Module (FHAM) 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 Diagnostic and Statistical Manual (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
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
VA Connecticut Healthcare System
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
Principal Investigator: Ismene L Petrakis, MD Yale University
  More Information

Publications:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00612352     History of Changes
Other Study ID Numbers: 0304025194
VA Alcohol Research Center ( Other Grant/Funding Number: VA Alcohol Research Center Grant )
P50AA012870 ( US NIH Grant/Contract Award Number )
Study First Received: December 27, 2007
Results First Received: January 3, 2017
Last Updated: January 3, 2017

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

ClinicalTrials.gov processed this record on April 21, 2017