Ketamine/Placebo Family History Positive Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Yale University
Sponsor:
Collaborator:
VA Connecticut Healthcare System
Information provided by (Responsible Party):
Ismene Petrakis, Yale University
ClinicalTrials.gov Identifier:
NCT00588952
First received: December 27, 2007
Last updated: May 27, 2014
Last verified: May 2014
  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
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: GABA Mechanisms Underlying the Vulnerability for Alcohol Dependence

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Positive and Negative Symptom Scale (PANSS), visual analog scales of mood states (i.e., anxiety) and the Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: Test day begins at Baseline, +15 minutes, +45 minutes, +80 minutes, +110 minutes, +170 minutes, +230 minutes ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Visual analog scales for high, similarity to ethanol, Mini Mental Status Examination (MMSE), placement of electrodes, Biphasic Alcohol Effects Scale, Hopkins Verbal Learning, number of drinks scale [ Time Frame: Baseline, +15 minutes, +45 minutes, +80 minutes, +110 minutes, +170 minutes, +230 minutes ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: March 2001
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ketamine
0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute for 60 minutes, IV Ketamine
Drug: Ketamine
Ketamine: 0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute for 60 minutes, IV
Placebo Comparator: Placebo
loading dose and an infusion for 60 minutes saline solution (Placebo)
Drug: Placebo
Placebo: loading dose and an infusion for 60 minutes saline solution

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 3 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 Positive and Negative Symptom Scale and the Clinician-Administered Dissociative States Scale to measure perceptual responses to ketamine, 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
Genders Eligible for Study:   Both
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
  3. For Family History Positive (FHP) Subjects: Biological father and another first or second-degree biological relative with history of alcoholism

Exclusion Criteria:

  1. 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
  8. 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

Contacts
Contact: Diana D. Limoncelli, BA 203-932-5711 ext 5217 diana.limoncelli@yale.edu

Locations
United States, Connecticut
VA Connecticut Healthcare System Recruiting
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
VA Connecticut Healthcare System
Investigators
Principal Investigator: Ismene L. Petrakis, MD Yale University
  More Information

Publications:
Responsible Party: Ismene Petrakis, Professor of Psychiatry, Yale University
ClinicalTrials.gov Identifier: NCT00588952     History of Changes
Other Study ID Numbers: 0103012310, VA Merit Grant - Petrakis
Study First Received: December 27, 2007
Last Updated: May 27, 2014
Health Authority: United States: Institutional Review Board

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
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
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 September 22, 2014