The study will evaluate the effects of the mGluR2/3 partial agonist LY2140023 (Pomaglumetad Methionil, "POMA") at selected doses on ketamine-stimulated glutamate release in prefrontal cortex as measured by pharmacoBOLD fMRI (also termed resting BOLD fMRI).
This study evaluates the effects of POMA at selected doses on ketamine-stimulated glutamate increase in the prefrontal cortex hypothesized to simulate the synaptic dysregulation that occurs endogenously in the pathogenesis of schizophrenia. The purpose of this is: 1) to determine whether the low dose (40 mg BID) utilized in recent (failed) clinical trials is sufficient to engage the primary target and 2) whether a higher (160 mg BID) dose, representing the maximum tolerated dose of POMA, engages the target to a greater degree. This study will further validate pharmacoBOLD as biomarker of mGluR2/3 target engagement, permitting its future use in other glutamatergic drug development.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
95
University of Alabama, Birmingham
Birmingham, Alabama, United States
University of California, Los Angeles
Los Angeles, California, United States
New York University
New York, New York, United States
Columbia University
New York, New York, United States
PharmacoBOLD change
pharmacoBOLD change, as summarized by the Amplitude measure
Time frame: Day 1 to Day 10
Brief Psychiatric Rating Scale (BPRS)
Clinical rating scale assessing common psychiatric symptoms
Time frame: Day 1 to Day 10
Clinician Administered Dissociative States Scale (CADSS)
Rates dissociative symptoms
Time frame: Day 1 to Day 10
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