Clinical trial NCT00588952: Ketamine/Placebo Family History Positive Study
Official title: NMDA Dysregulation in Individuals With a Family Vulnerability to 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: 2008-01-09
Enrollment: 99
Sex: ALL
Minimum age (years): 21
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: 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 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.

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

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)

Primary outcomes:
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
timeFrame: Baseline
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
timeFrame: 15 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
timeFrame: 45 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
timeFrame: 80 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
timeFrame: Baseline
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
timeFrame: 15 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
timeFrame: 45 minutes
measure: Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
timeFrame: 80 minutes
Secondary outcomes:
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: Yoon G, Pittman B, Limoncelli D, Krystal JH, Petrakis IL. Familial Alcoholism Risk and the Ratio of Stimulant to Sedative Effects of Ketamine. Biol Psychiatry. 2016 May 1;79(9):e69-e70. doi: 10.1016/j.biopsych.2015.09.006. Epub 2015 Sep 25. No abstract available.