N-Methyl-D-Aspartate (NMDA) Dysregulation in Individuals With a Family Vulnerability to Alcoholism - Full Text View

Sponsor:	Yale University
Information provided by:	Yale University
ClinicalTrials.gov Identifier:	NCT00588952

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: Ketamine Drug: Thiopental Drug: Placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Health Services Research
Official Title:	NMDA Dysregulation in Individuals With a Family Vulnerability to Alcoholism

Resource links provided by NLM:

MedlinePlus related topics: Alcoholism Anxiety

Drug Information available for: Thiopental sodium Thiopental Ketamine hydrochloride Ketamine

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

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: Test day begins at Baseline, +15 minutes, +45 minutes, +80 minutes, +110 minutes, +170 minutes, +230 minutes ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Visual analog scales for high, similarity to ethanol, Mini Mental Status Examination (MMSE), placement of electrodes, Biphasic Alcohol Effects Scale, Hopkins Verbal Learning, number of drinks scale [ Time Frame: Baseline, +15 minutes, +45 minutes, +80 minutes, +110 minutes, +170 minutes, +230 minutes ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	March 2001
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Ketamine 0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute for 60 minutes, IV Ketamine	Drug: Ketamine Ketamine: 0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute for 60 minutes, IV
Active Comparator: Thiopental 1.5 mg/kg, loading dose and an infusion rate of 40 mcg/kg/minute for 60 minutes, IV Thiopental	Drug: Thiopental Thiopental: 1.5 mg/kg, loading dose and an infusion rate of 40 mcg/kg/minute for 60 minutes
Placebo Comparator: Placebo loading dose and an infusion for 60 minutes saline solution (Placebo)	Drug: Placebo Placebo: loading dose and an infusion for 60 minutes saline solution

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 decrease 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 ketamine 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 the 60-minute intravenous infusion of placebo, ketamine, thiopental. Outcome measures include the Positive and Negative Symptom Scale and the Clinician-Administered Dissociative States Scale to measure perceptual responses to ketamine, and visual analog scales for mood states. Secondary measures include visual analog scales for high, similarity to ethanol, the Sensation Scale (a validated measure of ethanol-like sensations) and aspects of craving for alcohol.

Eligibility

Ages Eligible for Study:	21 Years to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Male and female between the ages of 21 and 30 years
Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories, absence of current and/or past substance abuse
For Family History Positive (FHP) Subjects: Biological father and another first or second-degree biological relative with history of alcoholism

Exclusion Criteria:

DSM-IV psychiatric and substance abuse diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (The Semi-Structured Assessment for the Genetics of alcoholism: SSAGA) and the Wisconsin Scales of Psychosis Proneness
History of counseling or psychotherapy; except family therapy centered around another family member
Extended unwillingness to remain alcohol-free for three days prior to testing and for the duration of the testing period
For women: positive pregnancy test at screening or intention to engage in unprotected sex during the study
Alcohol naïve
Previous bad experience with ketamine
Adoptee and no contact with family members
For Family History Negative (FHN) Subjects: NO family history of alcoholism in any first or second-degree relatives (subjects must reliably report on three first-degree relatives)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588952

Contacts

Contact: Diana D. Limoncelli, BA

203-932-5711 ext 5217

arc1@yale.edu

Locations

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

Sponsors and Collaborators

Yale University

Investigators

Principal Investigator:

Ismene L. Petrakis, MD

Yale University

More Information

No publications provided

Responsible Party:	Ismene Petrakis, Yale University
ClinicalTrials.gov Identifier:	NCT00588952 History of Changes
Other Study ID Numbers:	0103012310, 2P50-AA012870-07 NIAAA
Study First Received:	December 27, 2007
Last Updated:	January 6, 2009
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
N-Methylaspartate
Ketamine
Thiopental
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anesthetics, Dissociative

Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Hypnotics and Sedatives
GABA Modulators
GABA Agents
Anticonvulsants

ClinicalTrials.gov processed this record on February 09, 2012