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Ketamine/Placebo Family History Positive Study

This study has been completed.
Sponsor:
Collaborators:
VA Connecticut Healthcare System
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00588952
First received: December 27, 2007
Last updated: January 10, 2017
Last verified: January 2017
  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 and Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Outcomes Assessor)
Official Title: NMDA Dysregulation in Individuals With a Family Vulnerability to Alcoholism

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation [ Time Frame: Baseline ]
    Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation [ Time Frame: 15 minutes ]
    Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation [ Time Frame: 45 minutes ]
    Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation [ Time Frame: 80 minutes ]
    Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation [ Time Frame: Baseline ]
    Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation [ Time Frame: 15 minutes ]
    Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation [ Time Frame: 45 minutes ]
    Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol

  • Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation [ Time Frame: 80 minutes ]
    Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol


Enrollment: 99
Study Start Date: March 2001
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Family History Positive
Subjects with a positive family history of alcoholism
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
Other Name: intravenous
Experimental: Family History Negative
Subjects with a negative family history of alcoholism
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
Other Name: intravenous

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

Ages Eligible for Study:   21 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Connecticut
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
VA Connecticut Healthcare System
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
Principal Investigator: Ismene L. Petrakis, MD Yale University
  More Information

Publications:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00588952     History of Changes
Other Study ID Numbers: 0103012310
VA Alcohol Research Center ( Other Grant/Funding Number: VA Alcohol Research Center Grant )
P50AA012870 ( US NIH Grant/Contract Award Number )
Study First Received: December 27, 2007
Results First Received: January 10, 2017
Last Updated: January 10, 2017

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2017