Biomarker Assessment of Glutamatergic Target Engagement

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by New York State Psychiatric Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT02134951
First received: May 7, 2014
Last updated: NA
Last verified: April 2014
History: No changes posted
  Purpose

The purpose of this study is to assess the relative feasibility of 2 potential functional measures of target engagement (Glx MRS, BOLD fMRI) as well as EEG measures 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
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

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Compare changes in task-related fMRI BOLD response ("task related BOLD") in response to infusion of ketamine vs. placebo.


Estimated Enrollment: 15
Study Start Date: May 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (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, BOLD fMRI, and EEG to measure ketamine induced changes in glutamatergic indices. The investigators will recruit 20 subjects at each site in order to complete 15 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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 any prior exposure to ketamine or PCP
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02134951

Contacts
Contact: Jeffrey A Lieberman, MD 646-774-5300 jlieberman@nyspi.columbia.edu

Locations
United States, California
University of California Davis Not yet recruiting
Sacramento, California, United States, 95817
Contact: Cam Carter, MD    916-734-7783      
United States, Connecticut
Yale University Not yet recruiting
New Haven, Connecticut, United States, 06511
Contact: John Krystal, MD    203-785-6396      
United States, New York
New York State Psychiatric Institute Not yet recruiting
New York, New York, United States, 10032
Principal Investigator: Daniel Javitt, MD         
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Jeffrey A Lieberman, MD New York State Psychiatric Institute
  More Information

No publications provided

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
Study First Received: May 7, 2014
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 23, 2014