CClinicalTrials.gg
Sign In
CompletedNCT02134951Updated Aug 17, 2018Results posted

Biomarker Assessment of Glutamatergic Target Engagement

A Phase 4 interventional study of Ketamine and Normal saline in Healthy Controls, sponsored by New York State Psychiatric Institute. Completed at 3 sites in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-08-17.

Sponsored by New York State Psychiatric Institute · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
65
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Healthy Controls
03

In context

Lead sponsor

New York State Psychiatric Institute is the lead sponsor of 425 studies on the registry; 26 are open to participants now.

Of its 50 completed or terminated interventional studies of FDA-regulated products, 45 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
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

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
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
65 participants (actual)

Study arms

  • 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

  • Placebo comparator
    Placebo

    Placebo group will receive normal saline

    Drug: Normal saline

Interventions

  • DrugKetamine

    intravenous infusion of saline solution with ketamine

    Also known as: ketamine hydrochloride

  • DrugNormal saline

    Normal saline will be used for placebo in this group

    Also known as: saline

06

What researchers measure

Primary outcomes

  1. Glutamate + Glutamine (Glx) Response

    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.

    Time frame: Day 1

Other outcomes

  1. Pharmacological Blood-oxygen-level Dependent (pharmacoBOLD) Response

    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

    Time frame: Day 14

07

Results

Posted Feb 13, 2018

Participant flow

Participant flow — Overall Study
MilestoneKetaminePlacebo
Started3920
Completed3920
Not completed00

Outcome measures

PrimaryGlutamate + Glutamine (Glx) Response

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.

Time frame:
Day 1
Reported as:
Mean · Glx over creatinine ratio
Glutamate + Glutamine (Glx) Response
Glx over creatinine ratioKetaminePlacebo
Glutamate + Glutamine (Glx) Response0.015 ± .0020.007 ± .003
Other pre-specifiedPharmacological Blood-oxygen-level Dependent (pharmacoBOLD) Response

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

Time frame:
Day 14
Reported as:
Mean · BOLD signal units
Pharmacological Blood-oxygen-level Dependent (pharmacoBOLD) Response
BOLD signal unitsKetaminePlacebo
Pharmacological Blood-oxygen-level Dependent (pharmacoBOLD) Response.91 ± .1-0.27 ± 0.14

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ketamine0/39 (0%)0/39 (0%)6/39 (15.4%)
Placebo0/20 (0%)0/20 (0%)0/20 (0%)
Most frequent other events
Most frequent other events
EventKetaminePlacebo
ketamine psychological effectPsychiatric disorders6/390/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)KetaminePlaceboTotal
Mean31.1 ± 9.632.2 ± 10.231.5 ± 9.8
Sex: Female, Male
Sex: Female, Male(Participants)KetaminePlaceboTotal
Female211637
Male18422
08

Study locations

3 sites
  • University of California Davis
    Sacramento, California 95817, United States
  • Yale University
    New Haven, Connecticut 06511, United States
  • New York State Psychiatric Institute
    New York, New York 10032, United States
09

References and documents

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. PubMed 29167877 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 17, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02134951
Lead sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH)
Responsible party
Marlene Carlson (Manager, New York State Psychiatric Institute) — Principal investigator
First posted
May 9, 2014
Start date
May 2014
Primary completion
Oct 2015
Completion
Nov 2015
Results posted
Feb 13, 2018
Last update
Aug 17, 2018

Study contacts

Jeffrey A Lieberman, MD
principal investigator · New York State Psychiatric Institute

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

New York State Psychiatric Institute

Start the discussion