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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 : August 17, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Marlene Carlson, New York State Psychiatric Institute

Tracking Information
First Submitted Date  ICMJE May 7, 2014
First Posted Date  ICMJE May 9, 2014
Results First Submitted Date  ICMJE June 8, 2017
Results First Posted Date  ICMJE February 13, 2018
Last Update Posted Date August 17, 2018
Study Start Date  ICMJE May 2014
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2014)
Glx response [ Time Frame: Day 1 and Day 14 ]
Compare changes in Glx response to infusion of ketamine vs placebo, as measured by MRS.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2014)
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.
Current Other Pre-specified Outcome Measures
 (submitted: February 12, 2018)
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
Original Other Pre-specified Outcome Measures
 (submitted: May 7, 2014)
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.
 
Descriptive Information
Brief Title  ICMJE Biomarker Assessment of Glutamatergic Target Engagement
Official Title  ICMJE Biomarker Assessment of Glutamatergic Target Engagement
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Healthy Controls
Intervention  ICMJE
  • Drug: Ketamine
    intravenous infusion of saline solution with ketamine
    Other Name: ketamine hydrochloride
  • Drug: Normal saline
    Normal saline will be used for placebo in this group
    Other Name: saline
Study Arms  ICMJE
  • 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
    Intervention: Drug: Ketamine
  • Placebo Comparator: Placebo
    Placebo group will receive normal saline
    Intervention: Drug: Normal saline
Publications * Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Jan 1;75(1):11-19. doi: 10.1001/jamapsychiatry.2017.3572.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 3, 2015)
65
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2014)
15
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02134951
Other Study ID Numbers  ICMJE 6925
HHS-N-271-2012-0000-7-I ( Other Identifier: NIH/NIMH contract number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Marlene Carlson, New York State Psychiatric Institute
Study Sponsor  ICMJE New York State Psychiatric Institute
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Jeffrey A Lieberman, MD New York State Psychiatric Institute
PRS Account New York State Psychiatric Institute
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP