Ketamine/Placebo Family History Positive Study

This study is currently recruiting participants.
Verified February 2013 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: February 14, 2013
Last verified: February 2013

December 27, 2007
February 14, 2013
March 2001
July 2013   (final data collection date for primary outcome measure)
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 ]
Not Provided
Complete list of historical versions of study NCT00588952 on ClinicalTrials.gov Archive Site
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 ]
Not Provided
Not Provided
Not Provided
 
Ketamine/Placebo Family History Positive Study
GABA Mechanisms Underlying the Vulnerability for Alcohol Dependence

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Health Services Research
Alcoholism
  • Drug: Ketamine
    Ketamine: 0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute for 60 minutes, IV
  • Drug: Placebo
    Placebo: loading dose and an infusion for 60 minutes saline solution
  • Active Comparator: Ketamine
    0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute for 60 minutes, IV Ketamine
    Intervention: Drug: Ketamine
  • Placebo Comparator: Placebo
    loading dose and an infusion for 60 minutes saline solution (Placebo)
    Intervention: Drug: Placebo
Dickerson D, Pittman B, Ralevski E, Perrino A, Limoncelli D, Edgecombe J, Acampora G, Krystal JH, Petrakis I. Ethanol-like effects of thiopental and ketamine in healthy humans. J Psychopharmacol. 2010 Feb;24(2):203-11. doi: 10.1177/0269881108098612. Epub 2008 Nov 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
September 2013
July 2013   (final data collection date for primary outcome measure)

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)
Both
21 Years to 30 Years
Yes
Contact: Diana D. Limoncelli, BA 203-932-5711 ext 5217 diana.limoncelli@yale.edu
United States
 
NCT00588952
0103012310, VA Merit Grant - Petrakis
Yes
Ismene Petrakis, Yale University
Yale University
VA Connecticut Healthcare System
Principal Investigator: Ismene L. Petrakis, MD Yale University
Yale University
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP