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Ketamine/Placebo Family History Positive Study

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ClinicalTrials.gov Identifier: NCT00588952
Recruitment Status : Completed
First Posted : January 9, 2008
Results First Posted : March 3, 2017
Last Update Posted : October 6, 2021
Sponsor:
Collaborators:
VA Connecticut Healthcare System
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE December 27, 2007
First Posted Date  ICMJE January 9, 2008
Results First Submitted Date  ICMJE January 10, 2017
Results First Posted Date  ICMJE March 3, 2017
Last Update Posted Date October 6, 2021
Study Start Date  ICMJE March 2001
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2021)
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
  • 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 effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine/Placebo Family History Positive Study
Official Title  ICMJE NMDA Dysregulation in Individuals With a Family Vulnerability to Alcoholism
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Alcoholism
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Family History Positive
    Subjects with a positive family history of alcoholism
    Intervention: Drug: Ketamine and Placebo
  • Experimental: Family History Negative
    Subjects with a negative family history of alcoholism
    Intervention: Drug: Ketamine and Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2017)
99
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2008)
60
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00588952
Other Study ID Numbers  ICMJE 0103012310
VA Alcohol Research Center ( Other Grant/Funding Number: VA Alcohol Research Center Grant )
P50AA012870 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE
  • VA Connecticut Healthcare System
  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators  ICMJE
Principal Investigator: Ismene L. Petrakis, MD Yale University
PRS Account Yale University
Verification Date September 2021

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