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Biomarker Assessment of Glutamatergic Target Engagement

This study has been completed.
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
New York State Psychiatric Institute Identifier:
First received: May 7, 2014
Last updated: March 17, 2016
Last verified: March 2016
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.

Condition Intervention Phase
Healthy Controls Drug: Ketamine Drug: Normal saline Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Biomarker Assessment of Glutamatergic Target Engagement

Resource links provided by NLM:

Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Glx response [ Time Frame: Day 1 and Day 14 ]
    Compare changes in Glx response to infusion of ketamine vs placebo, as measured by MRS.

Secondary Outcome Measures:
  • Basal fMRI BOLD signal [ Time Frame: Day 1 and Day 14 ]
    Compare changes in basal fMRI BOLD signal ("pharmcoBOLD") in response to infusion of ketamine vs placebo.

Other Outcome Measures:
  • fMRI BOLD response [ Time Frame: Day 1 and Day 14 ]
    Compare changes in task-related fMRI BOLD response ("task related BOLD") in response to infusion of ketamine vs. placebo.

Enrollment: 65
Study Start Date: May 2014
Study Completion Date: November 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ketamine
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
Drug: Ketamine
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

Detailed Description:
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.

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Age 18-55
  • Negative Urine Toxicology
  • No present or past psychiatric conditions (including substance abuse or dependence, with the exception of nicotine dependence)
  • No family history of schizophrenia in a first-degree relative

Exclusion Criteria:

  • Any current DSM IV Axis I disorder and/or past substance abuse of dependence (nicotine dependence is allowed)
  • Any current use of amphetamines, opiates, cocaine, sedative-hypnotics, or cannabis
  • Current (i.e., within the last 3 months) treatment with any psychotropic medications
  • Pregnancy, lactation, or lack of use of effective birth control
  • Presence of positive history of significant medical or neurological illness (including any history of seizure), including high blood pressure (SBP >140, DBP >90), low blood pressure (SBP <100, DBP <60), orthostatic BP change>20% (1/3 SBP + 2/3 DBP) or cardiac illness or resting heart rate >100 or <50
  • History of significant violent behavior
  • History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated prior research ketamine studies will be eligible providing they have participated in no more than 5 previous research ketamine infusions. Subjects can have infusions not more frequently than biweekly and not more than 1/month on average, therefore subjects entering the study will need to wait 1 month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
  • Contraindication to MRI scanning, including metal implants or claustrophobia. Metal implants, pacemaker, other metal (e.g. shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects", F.G. Shellock, Lippincott Williams and Wilkins NY 2001
  • Color Blindness
  Contacts and Locations
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Please refer to this study by its identifier: NCT02134951

United States, California
University of California Davis
Sacramento, California, United States, 95817
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06511
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
National Institute of Mental Health (NIMH)
Principal Investigator: Jeffrey A Lieberman, MD New York State Psychiatric Institute
  More Information

Responsible Party: New York State Psychiatric Institute Identifier: NCT02134951     History of Changes
Other Study ID Numbers: 6925
HHS-N-271-2012-0000-7-I ( Other Identifier: NIH/NIMH contract number )
Study First Received: May 7, 2014
Last Updated: March 17, 2016

Additional relevant MeSH terms:
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action processed this record on August 17, 2017