Biomarker Assessment of Glutamatergic Target Engagement

Healthy Controls Clinical Trial

Official title:

Biomarker Assessment of Glutamatergic Target Engagement

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02134951
• Other study ID #: 6925
• Secondary ID: HHS-N-271-2012-0
• Status: Completed
• Phase: Phase 4
• Start date: May 2014
• Est. completion date: November 2015

Study information

• Verified date: August 2018
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: November 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Controls

Intervention

Drug:
• Ketamine
intravenous infusion of saline solution with ketamine
• Normal saline
Normal saline will be used for placebo in this group

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut
United States	New York State Psychiatric Institute	New York	New York
United States	University of California Davis	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Day 14
Primary	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.	Day 1