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.

Study Overview

• Status: Completed
• Conditions: Alcoholism
• Intervention / Treatment: Drug: Ethanol High Dose, Ethanol Low Dose, and Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Drinks Felt Consumed at Baseline	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.	Baseline
Number of Drinks Felt Consumed at 10 Minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.	10 minutes
Number of Drinks Felt Consumed at 30 Minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.	30 minutes
Number of Drinks Felt Consumed at 110 Minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.	110 minutes
Number of Drinks Felt Consumed at 140 Minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.	140 minutes
Number of Drinks Felt Consumed at 170 Minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.	170 minutes
Number of Drinks Felt Consumed at 230 Minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.	230 minutes
Visual Analog Scale of Similarity to Alcohol - 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	Baseline
Visual Analog Scale of Similarity to Alcohol -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	10 minutes
Visual Analog Scale of Similarity to Alcohol - 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	30 minutes
Visual Analog Scale of Similarity to Alcohol - 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	60 minutes
Visual Analog Scale of Similarity to Alcohol - 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	110 minutes
Visual Analog Scale of Similarity to Alcohol - 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	140 minutes
Visual Analog Scale of Similarity to Alcohol - 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	170 minutes
Visual Analog Scale of Similarity to Alcohol - 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	230 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 10 Minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	10 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 30 Minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	30 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 60 Minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	60 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 140 Minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	140 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)	230 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 10 Minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	10 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 30 Minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	30 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 60 Minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	60 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 110 Minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 140 Minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	140 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 240 Minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)	240 minutes
Visual Analog Scale (VAS) HIGH - Baseline	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	Baseline
Visual Analog Scale (VAS) HIGH - 10 Minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	10 minutes
Visual Analog Scale (VAS) HIGH - 30 Minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	30 minutes
Visual Analog Scale (VAS) HIGH - 60 Minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	60 minutes
Visual Analog Scale (VAS) HIGH - 110 Minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	110 minutes
Visual Analog Scale (VAS) HIGH - 140 Minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	140 minutes
Visual Analog Scale (VAS) HIGH - 170 Minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	170 minutes
Visual Analog Scale (VAS) HIGH - 240 Minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)	240 minutes
Visual Analog Scale (VAS) Drowsy - Baseline	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	Baseline
Visual Analog Scale (VAS) Drowsy - 10 Minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	10 minutes
Visual Analog Scale (VAS) Drowsy - 30 Minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	30 minutes
Visual Analog Scale (VAS) Drowsy - 60 Minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	60 minutes
Visual Analog Scale (VAS) Drowsy - 110 Minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	110 minutes
Visual Analog Scale (VAS) Drowsy - 140 Minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	140 minutes
Visual Analog Scale (VAS) Drowsy - 170 Minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	170 minutes
Visual Analog Scale (VAS) Drowsy - 230 Minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)	230 minutes
Hopkins Verbal Learning Task - Immediate Recall - 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)	30 minutes - Trial 1
Hopkins Verbal Learning Task - Immediate Recall - 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)	30 minutes - Trial 2
Hopkins Verbal Learning Task - Immediate Recall - 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)	30 minutes - Trial 3
Hopkins Verbal Learning Task - Delay Recall	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)	60 minutes
Pegboard Task - Baseline (Dominant Hand)	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	Baseline
Pegboard Task - 30 Minutes (Dominant Hand)	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.	30 minutes
Pegboard Task - Baseline (Non-Dominant Hand)	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.	Baseline
Pegboard Task - 30 Minuites (Non-Dominant Hand)	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.	30 minutes

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); VA Connecticut Healthcare System

Publications and helpful links

General Publications

• Ralevski E, Perrino A, Acampora G, Koretski J, Limoncelli D, Petrakis I. Analgesic effects of ethanol are influenced by family history of alcoholism and neuroticism. Alcohol Clin Exp Res. 2010 Aug;34(8):1433-41. doi: 10.1111/j.1530-0277.2010.01228.x. Epub 2010 May 21.
• Perrino AC Jr, Ralevski E, Acampora G, Edgecombe J, Limoncelli D, Petrakis IL. Ethanol and pain sensitivity: effects in healthy subjects using an acute pain paradigm. Alcohol Clin Exp Res. 2008 Jun;32(6):952-8. doi: 10.1111/j.1530-0277.2008.00653.x. Epub 2008 Apr 26.

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: December 27, 2007
• First Submitted That Met QC Criteria: January 25, 2008
• First Posted (Estimate): February 11, 2008

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: 0304025194; VA Alcohol Research Center (Other Grant/Funding Number: VA Alcohol Research Center Grant); P50AA012870 (U.S. NIH Grant/Contract)