Ketamine/Placebo Family History Positive Study

NCT ID: NCT00588952

Last Updated: 2021-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 99 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 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.

Conditions

Alcoholism

Study Design

• Allocation Method: 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: EXPERIMENTAL

Ketamine and Placebo

Intervention Type: DRUG

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

Family History Negative

Subjects with a negative family history of alcoholism

Group Type: EXPERIMENTAL

Ketamine and Placebo

Intervention Type: DRUG

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

Interventions

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

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

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)

• 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

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.

Reference Type: BACKGROUND

PMID: 26475672 (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

0103012310

Identifier Type: -

Identifier Source: org_study_id