Ketamine/Placebo Family History Positive Study

Alcoholism Clinical Trial

Official title:

NMDA Dysregulation in Individuals With a Family Vulnerability to Alcoholism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00588952
• Other study ID #: 0103012310
• Secondary ID: VA Alcohol Resea
• Status: Completed
• Phase: N/A
• Start date: March 2001
• Est. completion date: June 2015

Study information

• Verified date: September 2021
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 30 Years

Eligibility

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)

Related Conditions & MeSH terms

• Alcoholism

Intervention

Drug:
• Ketamine and Placebo
Two test days will involve administration of placebo and Ketamine (0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute) intravenously for 60 minutes

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (3)

Lead Sponsor	Collaborator
Yale University	National Institute on Alcohol Abuse and Alcoholism (NIAAA), VA Connecticut Healthcare System

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation	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.	Baseline
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation	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.	15 minutes
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation	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.	45 minutes
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation	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.	80 minutes
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation	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.	Baseline
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation	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.	15 minutes
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation	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.	45 minutes
Primary	Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation	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.	80 minutes