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The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects (GuaKet)

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ClinicalTrials.gov Identifier: NCT01600885
Recruitment Status : Completed
First Posted : May 17, 2012
Results First Posted : October 28, 2014
Last Update Posted : August 21, 2017
Sponsor:
Collaborator:
VA Office of Research and Development
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE May 15, 2012
First Posted Date  ICMJE May 17, 2012
Results First Submitted Date  ICMJE August 29, 2014
Results First Posted Date  ICMJE October 28, 2014
Last Update Posted Date August 21, 2017
Study Start Date  ICMJE August 2008
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 22, 2014)
  • Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Inferior Parietal Lobule [ Time Frame: Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion ]
    Scans will be analyzed for task-related prefrontal activation Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline)
  • Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Middle Frontal Gyrus [ Time Frame: Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion ]
    Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline)
  • Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Superior Frontal Gyrus [ Time Frame: Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion ]
    Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline)
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2012)
Functional magnetic resonance imaging [ Time Frame: Within 4 hours of dose administration ]
Scans will be analyzed for task-related prefrontal activation
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2012)
Task performance [ Time Frame: Within 4 hours of dose administration ]
During the fMRI scans, subjects will be asked to complete a spatial task that utilizes Working Memory.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects
Official Title  ICMJE The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects
Brief Summary

The purpose of the study is

  1. To establish the feasibility of fMRI studies of the interaction of guanfacine and ketamine.
  2. To explore the possibility that guanfacine can ameliorate the negative effects of ketamine on task-related prefrontal activation.
  3. To assess the strength of any interaction between guanfacine and ketamine.
Detailed Description

Potential subjects will be interviewed over the phone and, if appropriate, will be scheduled for a screening session. Participants who meet study criteria will participate in two study sessions separated by at least two weeks. The sessions will be identical except on one day they will receive guanfacine and on the other, they will receive a placebo.

This study was initially completed in 2014. Upon analysis of the collected data, it was decided to add additional subjects and gather additional data to verify results seen in the collected data. The study was reopened and new data was added beginning in September 2016. Information about the study beginning in 2016 is available in a separate record.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE NMDA Receptor Function
Intervention  ICMJE
  • Drug: Guanfacine
    Subjects will be given 3mg of guanfacine before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) will be given during the visual fixation scan. Immediately after completion of the 1 min bolus, the participant will receive a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation will be measured during a spatial working memory task. The entire scan will last approximately two and a half hours and the ketamine infusion will be up to one hour and 15 minutes.
  • Drug: Placebo
    Subjects will be given a placebo before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) will be given during the visual fixation scan. Immediately after completion of the 1 min bolus, the participant will receive a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation will be measured during a spatial working memory task. The entire scan will last approximately two and a half hours and the ketamine infusion will be up to one hour and 15 minutes.
Study Arms  ICMJE
  • Active Comparator: Guanfacine then Placebo
    During the first study session, the participant will receive guanfacine before undergoing a ketamine-infusion fMRI. During the second study session, at least two weeks later, the participant will receive a placebo before undergoing a ketamine-infusion fMRI.
    Interventions:
    • Drug: Guanfacine
    • Drug: Placebo
  • Active Comparator: Placebo then Guanfacine
    During the first study session, the participant will receive a placebo before undergoing a ketamine-infusion fMRI. During the second study session, at least two weeks later, the participant will receive guanfacine before undergoing a ketamine-infusion fMRI.
    Interventions:
    • Drug: Guanfacine
    • Drug: Placebo
Publications *

*   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: July 20, 2017)
16
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2012)
20
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age between 21 and 45, inclusive
  • Right-handed
  • Have at least a 12th grade education level or equivalent
  • Able to read and write English as a primary language
  • Willing to refrain from caffeine and alcohol use for one week prior to each MRI session.

Exclusion Criteria:

  • Abnormality on physical examination
  • A 12 lead ECG at screening has clinically significant abnormalities as determined by the physician reading the ECG
  • A positive pre-study urine drug screen or, at the study physicians' discretion on any drug screens given before the scans
  • Abnormality on clinical chemistry or hematology examination at the pre-study medical screening.
  • History of positive HIV or Hepatitis B.
  • Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within the week prior to the MRI scan.
  • History of any substance abuse disorder meeting DSM-IV criteria with the exception of nicotine
  • Any history of DSM-IV Axis I psychiatric disorders,
  • Any history of major medical or neurological disorders
  • Any history indicating learning disability, mental retardation, or attention deficit disorder.
  • First-degree relative with Axis I DSM-IV disorder including substance abuse or dependence.
  • Any clinically significant abnormalities on screening electrocardiogram
  • Any history of head injury
  • Any evidence of psychosis-like symptoms, as indicated by elevated scores on the Perceptual Aberration-Magical Ideation (Chapman, Chapman et al. 1978; Eckblad, Chapman et al. 1983) and the revised Social Anhedonia scales(Eckblad, Chapman et al. unpublished)
  • A positive urine toxicology screen for illicit substance use or positive alcohol breathalyzer test conducted at screening interview and prior to each MRI session
  • Known sensitivity to ketamine.
  • Body circumference of 52 inches or greater.
  • History of claustrophobia
  • Any clinically significant impairment of color vision or visual acuity after correction available in the scanner.
  • Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire
  • Pregnancy or breast-feeding would exclude potential participants and all female subjects will receive a urine pregnancy test at screening and before each MRI scan.
  • Donation of blood in excess of 500 mL within 56 days prior to dosing.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Blood pressure must be higher than 90/70. Pulse must be greater than 40 unless the participant is cleared by a study physician
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 45 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 NCT01600885
Other Study ID Numbers  ICMJE 0807004092
Has Data Monitoring Committee No
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 Office of Research and Development
Investigators  ICMJE
Principal Investigator: John H Krystal, M.D. Yale University
Study Director: Naomi R Driesen, Ph.D. Yale University
PRS Account Yale University
Verification Date July 2017

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