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

NCT ID: NCT00612352

Last Updated: 2021-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-03-31
• Study Completion Date: 2015-06-30

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.

Conditions

Alcoholism

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Family HIstory Positive

Subjects with a positive family history of alcoholism.

Group Type: ACTIVE_COMPARATOR

Ethanol High Dose, Ethanol Low Dose, and Placebo

Intervention Type: DRUG

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.

Family History Negative

Subjects with a negative family history of alcoholism.

Group Type: ACTIVE_COMPARATOR

Ethanol High Dose, Ethanol Low Dose, and Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

intravenous

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

VA Connecticut Healthcare System

FED

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ismene L Petrakis, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 20497133 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18445106 (View on PubMed)

Other Identifiers

VA Alcohol Research Center

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P50AA012870

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0304025194

Identifier Type: -

Identifier Source: org_study_id