Biomarker Assessment of Glutamatergic Target Engagement
The purpose of this study is to assess the relative feasibility of 2 potential functional measures of target engagement (Glx MRS, BOLD fMRI) to systematically assess mGluR 2/3 in drug development for psychotic spectrum disorders.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Biomarker Assessment of Glutamatergic Target Engagement|
- Glx response [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]Compare changes in Glx response to infusion of ketamine vs placebo, as measured by MRS.
- Basal fMRI BOLD signal [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]Compare changes in basal fMRI BOLD signal ("pharmcoBOLD") in response to infusion of ketamine vs placebo.
- fMRI BOLD response [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]Compare changes in task-related fMRI BOLD response ("task related BOLD") in response to infusion of ketamine vs. placebo.
|Study Start Date:||May 2014|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
IV infusion of ketamine 0.23mg/kg bolus over 1 minutes followed by 0.58 mg/kg/hr over 30 minutes then 0.29mg/kg/hr over 64 minutes
intravenous infusion of saline solution with ketamine
Other Name: ketamine hydrochloride
Placebo Comparator: Placebo
Placebo group will receive normal saline
Drug: Normal saline
Normal saline will be used for placebo in this group
Other Name: saline
This is a pilot study of healthy subject to assess the feasibility of Glx MRS and BOLD fMRI to measure ketamine induced changes in glutamatergic indices. The investigators will randomize 18 subjects at each site. Subjects will be randomized to ketamine or placebo in a 2:1 ratio and receive two drug challenges separated by at least two weeks. Ketamine challenge is used to induce a "glutamate surge" within prefrontal brain regions that can be detected using neurochemical and functional imaging techniques. Each subject will receive MRS and BOLD fMRI during each challenge day. The goal of the pilot study is to assess the feasibility of both the proposed ketamine challenge paradigm and of the proposed imaging-based biomarkers. Specific indices to be used in assessing feasibility will include effect size, cross-site and cross-subject reliability, safety, and subject tolerability as similar studies will be performed independently at Yale and UC Davis. Second this information will be used to select and refine final study parameters for a subsequent full proof-of-clinical mechanism (POCM) study investigating the effect of Pomaglumetad on ketamine-induced MRS and fMRI effects.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02134951
|Contact: Marlene M Carlson, MPHfirstname.lastname@example.org|
|United States, California|
|University of California Davis||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Cam Carter, MD 916-734-7783|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06511|
|Contact: John Krystal, MD 203-785-6396|
|United States, New York|
|New York State Psychiatric Institute||Recruiting|
|New York, New York, United States, 10032|
|Principal Investigator: Daniel Javitt, MD|
|Principal Investigator:||Jeffrey A Lieberman, MD||New York State Psychiatric Institute|