Ketamine/Placebo Family History Positive Study

Not Applicable

Completed

• Conditions: Alcoholism
• Interventions: Drug: Ketamine and Placebo

• Registration Number: NCT00588952
• Lead Sponsor: Yale University

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 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 2 test days in a randomized balanced order under double-blind conditions. Test days will involve the 60-minute intravenous infusion of placebo and ketamine. Outcome measures include the Biphasic Alcohol Scale 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.

Study Timeline

• Study Start: 2001-03
• Study First Submitted: 2007-12-27
• Study First Submitted QC: 2008-01-08
• Study First Posted: 2008-01-09
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Results First Submitted: 2017-01-10
• Results First Submitted QC: 2017-01-10
• Results First Posted: 2017-03-03
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-09
• Last Update Posted: 2021-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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

For Family History Positive (FHP) Subjects: Biological father and another first or second-degree biological relative with history of alcoholism

Exclusion Criteria

1. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (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
2. History of counseling or psychotherapy; except family therapy centered around another family member
3. Extended unwillingness to remain alcohol-free for three days prior to testing and for the duration of the testing period
4. For women: positive pregnancy test at screening or intention to engage in unprotected sex during the study
5. Alcohol naïve
6. Previous bad experience with ketamine
7. 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Family History Positive	Ketamine and Placebo	Subjects with a positive family history of alcoholism
Family History Negative	Ketamine and Placebo	Subjects with a negative family history of alcoholism

Primary Outcome Measures

Name	Time	Method
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation	80 minutes	Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation	80 minutes	Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.

Trial Locations

Locations (1)

VA Connecticut Healthcare System; 🇺🇸 West Haven, Connecticut, United States