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Biomarker Assessment of Glutamatergic Target Engagement

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ClinicalTrials.gov Identifier: NCT02134951
Recruitment Status : Completed
First Posted : May 9, 2014
Results First Posted : February 13, 2018
Last Update Posted : February 13, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
New York State Psychiatric Institute

Brief Summary:
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 or disease Intervention/treatment Phase
Healthy Controls Drug: Ketamine Drug: Normal saline Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Biomarker Assessment of Glutamatergic Target Engagement
Study Start Date : May 2014
Actual Primary Completion Date : October 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine
U.S. FDA Resources

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. Glutamate + Glutamine (Glx) Response [ Time Frame: Day 1 ]
    Compare changes in Glx response to infusion of ketamine vs placebo, as measured by proton magnetic resonance spectroscopy (¹H MRS). Calculated by post-pre changes in the Glx over creatinine ratios, with higher values indicating higher Glx/creatinine ratios.


Other Outcome Measures:
  1. Pharmacological Blood-oxygen-level Dependent (pharmacoBOLD) Response [ Time Frame: Day 14 ]
    Compare changes inpharmacoBOLD in response to infusion of ketamine vs. placebo, as measured by resting state functional magnetic resonance imaging. Calculated by post-pre changes, with higher values indicating higher response



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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02134951


Locations
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)
Investigators
Principal Investigator: Jeffrey A Lieberman, MD New York State Psychiatric Institute

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT02134951     History of Changes
Other Study ID Numbers: 6925
HHS-N-271-2012-0000-7-I ( Other Identifier: NIH/NIMH contract number )
First Posted: May 9, 2014    Key Record Dates
Results First Posted: February 13, 2018
Last Update Posted: February 13, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action