Clinical trial NCT00612352: Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism
Official title: Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcoholism
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: VA Connecticut Healthcare System
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2008-02-11
Enrollment: 180
Sex: ALL
Minimum age (years): 21
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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 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.

Primary outcomes:
measure: Number of Drinks Felt Consumed at Baseline
timeFrame: Baseline
measure: Number of Drinks Felt Consumed at 10 Minutes
timeFrame: 10 minutes
measure: Number of Drinks Felt Consumed at 30 Minutes
timeFrame: 30 minutes
measure: Number of Drinks Felt Consumed at 110 Minutes
timeFrame: 110 minutes
measure: Number of Drinks Felt Consumed at 140 Minutes
timeFrame: 140 minutes
measure: Number of Drinks Felt Consumed at 170 Minutes
timeFrame: 170 minutes
measure: Number of Drinks Felt Consumed at 230 Minutes
timeFrame: 230 minutes
measure: Visual Analog Scale of Similarity to Alcohol - Baseline
timeFrame: Baseline
measure: Visual Analog Scale of Similarity to Alcohol -10 Minutes
timeFrame: 10 minutes
measure: Visual Analog Scale of Similarity to Alcohol - 30 Minutes
timeFrame: 30 minutes
measure: Visual Analog Scale of Similarity to Alcohol - 60 Minutes
timeFrame: 60 minutes
measure: Visual Analog Scale of Similarity to Alcohol - 110 Minutes
timeFrame: 110 minutes
measure: Visual Analog Scale of Similarity to Alcohol - 140 Minutes
timeFrame: 140 minutes
measure: Visual Analog Scale of Similarity to Alcohol - 170 Minutes
timeFrame: 170 minutes
measure: Visual Analog Scale of Similarity to Alcohol - 230 Minutes
timeFrame: 230 minutes
Secondary outcomes:
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline
timeFrame: Baseline
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 10 Minutes
timeFrame: 10 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 30 Minutes
timeFrame: 30 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 60 Minutes
timeFrame: 60 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes
timeFrame: 110 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 140 Minutes
timeFrame: 140 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes
timeFrame: 170 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes
timeFrame: 230 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline
timeFrame: Baseline
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 10 Minutes
timeFrame: 10 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 30 Minutes
timeFrame: 30 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 60 Minutes
timeFrame: 60 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 110 Minutes
timeFrame: 110 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 140 Minutes
timeFrame: 140 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes
timeFrame: 170 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 240 Minutes
timeFrame: 240 minutes
measure: Visual Analog Scale (VAS) HIGH - Baseline
timeFrame: Baseline
measure: Visual Analog Scale (VAS) HIGH - 10 Minutes
timeFrame: 10 minutes
measure: Visual Analog Scale (VAS) HIGH - 30 Minutes
timeFrame: 30 minutes
measure: Visual Analog Scale (VAS) HIGH - 60 Minutes
timeFrame: 60 minutes
measure: Visual Analog Scale (VAS) HIGH - 110 Minutes
timeFrame: 110 minutes
measure: Visual Analog Scale (VAS) HIGH - 140 Minutes
timeFrame: 140 minutes
measure: Visual Analog Scale (VAS) HIGH - 170 Minutes
timeFrame: 170 minutes
measure: Visual Analog Scale (VAS) HIGH - 240 Minutes
timeFrame: 240 minutes
measure: Visual Analog Scale (VAS) Drowsy - Baseline
timeFrame: Baseline
measure: Visual Analog Scale (VAS) Drowsy - 10 Minutes
timeFrame: 10 minutes
measure: Visual Analog Scale (VAS) Drowsy - 30 Minutes
timeFrame: 30 minutes
measure: Visual Analog Scale (VAS) Drowsy - 60 Minutes
timeFrame: 60 minutes
measure: Visual Analog Scale (VAS) Drowsy - 110 Minutes
timeFrame: 110 minutes
measure: Visual Analog Scale (VAS) Drowsy - 140 Minutes
timeFrame: 140 minutes
measure: Visual Analog Scale (VAS) Drowsy - 170 Minutes
timeFrame: 170 minutes
measure: Visual Analog Scale (VAS) Drowsy - 230 Minutes
timeFrame: 230 minutes
measure: Hopkins Verbal Learning Task - Immediate Recall - Trial 1
timeFrame: 30 minutes - Trial 1
measure: Hopkins Verbal Learning Task - Immediate Recall - Trial 2
timeFrame: 30 minutes - Trial 2
measure: Hopkins Verbal Learning Task - Immediate Recall - Trial 3
timeFrame: 30 minutes - Trial 3
measure: Hopkins Verbal Learning Task - Delay Recall
timeFrame: 60 minutes
measure: Pegboard Task - Baseline (Dominant Hand)
timeFrame: Baseline
measure: Pegboard Task - 30 Minutes (Dominant Hand)
timeFrame: 30 minutes
measure: Pegboard Task - Baseline (Non-Dominant Hand)
timeFrame: Baseline
measure: Pegboard Task - 30 Minuites (Non-Dominant Hand)
timeFrame: 30 minutes
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: Yale University
name: Ismene L Petrakis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.