Clinical trial NCT02919774: Pomaglumetad Effects on Glutamate Biomarkers
Official title: Biomarker Assessment of Pomaglumetad on Glutamate Targets: Proof of Clinical Mechanism of Action (POCM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Controls
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2016-09-29
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Medically healthy
* Capable of understanding the study procedures and able to provide informed consent
* Men and women must agree to use a reliable method of birth control during the study. Women who are post-menopausal or otherwise not of childbearing potential are also eligible

Exclusion Criteria:

* Current or past Axis I psychiatric history
* Positive urine toxicology
* History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated in prior research ketamine studies will be eligible. 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 one month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
* History of first-degree relative with schizophrenia
* History of violence
* Presence or positive history of significant medical illness
* Presence or positive history neurological illness or any other disease/procedure/accident/intervention association with significant injury to or malfunction of the central nervous system (CNS) or history of significant head injury
* Pregnancy or breast feeding
* Metal implants, pacemaker, other metal or paramagnetic objects contained within the body
* Medicinal patch, unless removed prior to MRI scan
* Currently taking any psychotropic medication, including antidepressant medications, benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic medications and stimulants.
* Claustrophobia
* Suicidal ideation with intent or plan in the 6 months prior to screening
* Weight \> 86.95 kg (191.2 lbs)
* Subthreshold pharmacoBOLD response during screening ketamine infusion

Primary outcomes:
measure: PharmacoBOLD change
timeFrame: Day 1 to Day 10
Secondary outcomes:
measure: Brief Psychiatric Rating Scale (BPRS)
timeFrame: Day 1 to Day 10
measure: Clinician Administered Dissociative States Scale (CADSS)
timeFrame: Day 1 to Day 10
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Jeffrey A Lieberman, MD
role: PRINCIPAL_INVESTIGATOR
References: