Pomaglumetad Effects on Glutamate Biomarkers

Healthy Controls Clinical Trial

Official title:

Biomarker Assessment of Pomaglumetad on Glutamate Targets: Proof of Clinical Mechanism of Action (POCM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02919774
• Other study ID #: 7285
• Secondary ID: 271201200007I-4-
• Status: Completed
• Phase: Phase 1
• Start date: October 2016
• Est. completion date: May 25, 2018

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: May 25, 2018
• Est. primary completion date: April 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Controls

Intervention

Drug:
• POMA
Pomaglumetad ("POMA") is a mGluR 2/3 partial agonist
• placebo
matching placebo tablets

Locations

Country	Name	City	State
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	University of California, Los Angeles	Los Angeles	California
United States	Columbia University	New York	New York
United States	New York University	New York	New York

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
Primary	PharmacoBOLD change	pharmacoBOLD change, as summarized by the Amplitude measure	Day 1 to Day 10
Secondary	Brief Psychiatric Rating Scale (BPRS)	Clinical rating scale assessing common psychiatric symptoms	Day 1 to Day 10
Secondary	Clinician Administered Dissociative States Scale (CADSS)	Rates dissociative symptoms	Day 1 to Day 10