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Trial record 1 of 1 for:    17460065 [PUBMED-IDS]
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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition NMDA Receptor Function
Interventions Drug: Guanfacine
Drug: Placebo
Enrollment 16

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Guanfacine Then Placebo Placebo Then Guanfacine
Hide Arm/Group Description

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.

Guanfacine then Placebo: During the first study session, the patient 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.

The second study session will be identical except that the patient will be given a placebo instead of the 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.

Placebo then Guanfacine: During the first study session, the patient 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.

The second study session will be identical except that the patient will be given 3mg of guanfacine instead of the placebo.

Period Title: First Period
Started 10 9
Completed 8 8
Not Completed 2 1
Reason Not Completed
Adverse Event             1             1
moved out of area             1             0
Period Title: Wash Out Period
Started 8 8
Completed 8 8
Not Completed 0 0
Period Title: Second Period
Started 8 8
Completed 8 8
Not Completed 0 0
Arm/Group Title Overall Study
Hide Arm/Group Description This 'arm' consists of all study participants who started the first Study Period. This Study Period consisted of an initial screening visit in which it was determined whether participants met the inclusion/exclusion criteria for further participation in this study.
Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
Baseline population is the number of participants who started the study
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants
30  (6.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
9
  47.4%
Male
10
  52.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Hispanic or Latino
2
  10.5%
Not Hispanic or Latino
17
  89.5%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   5.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
  15.8%
White
13
  68.4%
More than one race
0
   0.0%
Unknown or Not Reported
2
  10.5%
1.Primary Outcome
Title Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Inferior Parietal Lobule
Hide Description

Scans will be analyzed for task-related prefrontal activation

Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline)

Time Frame Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ALL SUBJECTS WHO COMPLETED THE STUDY WERE INCLUDED IN ANALYSIS
Arm/Group Title Guanfacine Placebo
Hide Arm/Group Description:
Subjects were given 3mg of guanfacine before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the subjects received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes.
Subjects were given a placebo before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the participant received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes.
Overall Number of Participants Analyzed 16 16
Mean (Standard Error)
Unit of Measure: percent change in saline signal
-0.17  (0.046) -0.094  (0.054)
2.Primary Outcome
Title Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Middle Frontal Gyrus
Hide Description Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline)
Time Frame Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ALL SUBJECTS WHO COMPLETED THE STUDY WERE INCLUDED IN ANALYSIS
Arm/Group Title Guanfacine Placebo
Hide Arm/Group Description:
Subjects were given 3mg of guanfacine before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the subjects received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes.
Subjects were given a placebo before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the participant received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes.
Overall Number of Participants Analyzed 16 16
Mean (Standard Error)
Unit of Measure: percent change in saline signal
-0.1  (0.052) 0.052  (0.0652)
3.Primary Outcome
Title Percent Change in Amelioration of Ketamine-related Task Activation as Measured by Functional Magnetic Resonance Imaging in Superior Frontal Gyrus
Hide Description Difference Score: Percent Signal Change in Regions of Interest (ketamine - saline)
Time Frame Within 4 hours of dose administration, after up to 1.25 hours of ketamine infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ALL SUBJECTS WHO COMPLETED THE STUDY WERE INCLUDED IN ANALYSIS
Arm/Group Title Guanfacine Placebo
Hide Arm/Group Description:
Subjects were given 3mg of guanfacine before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the subjects received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes.
Subjects were given a placebo before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the participant received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes.
Overall Number of Participants Analyzed 16 16
Mean (Standard Error)
Unit of Measure: percent change in saline signal
-0.134  (0.0413) -0.086  (0.0365)
Time Frame Throughout the length of the study (Aproximately 3 years)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Guanfacine Placebo
Hide Arm/Group Description Subjects were given 3mg of guanfacine before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the subjects received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes. Subjects were given 3mg of guanfacine before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) was given during the visual fixation scan. Immediately after completion of the 1 min bolus, the subjects received a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation was measured during a spatial working memory task. The entire scan lasted approximately two and a half hours and the ketamine infusion lasted up to one hour and 15 minutes.
All-Cause Mortality
Guanfacine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/19 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Guanfacine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/19 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Guanfacine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/19 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: John Krystal, MD
Organization: Yale University
Phone: 203-785-6396
Publications:
Brandt, J. The Hopkins Verbal Learning Test: development of a new memory test with six equivalent forms The Clinical Neuropsychologist 125-142, 1991
Kaye, S., L. Opler, et al. (1986) Positive and Negative Syndrome Scale. Toronto, Ontario. Multi-Health Systems, Inc.
Newcomer, J., N. Farber, et al. (1999).
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01600885     History of Changes
Other Study ID Numbers: 0807004092
First Submitted: May 15, 2012
First Posted: May 17, 2012
Results First Submitted: August 29, 2014
Results First Posted: October 28, 2014
Last Update Posted: August 21, 2017