Glutamate Reducing Interventions in Schizophrenia

Study Overview
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Brief Summary
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Participants will be administered several doses of pomaglumetad (POMA) (low and high doses) over 14 days to individuals at clinical high risk for developing psychosis and use magnetic resonance imaging (MRI) brain imaging to determine whether these doses of POMA are affecting glutamate levels.

Detailed Description
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A double-blind, randomized, phase 1b, multiple dose trial of 14 days of treatment with POMA (80 mg, 160 mg, 240 mg, 320 mg) in clinical high risk patients to determine which dose, if any, reduces glutamate and metabolism using MRI techniques. The GO NO-GO decision will be whether or not any dose tested in the R61 phase of the trial decreases left hippocampal CA1 region cerebral blood volume (CBV).

Official Title
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Glutamate Reducing Interventions in Schizophrenia

Conditions
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Clinical High Risk for Psychosis

Intervention / Treatment
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* Drug: Pomaglumetad methionil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capacity to provide informed consent Currently using a reliable form of birth control Exclusion Criteria: Metal implants in body or a history of metal working Lifetime diagnosis of asthmatic symptoms within the past 3 years or known sensitivity to contrast agents Lifetime diagnosis of renal failure/disease Acute neurological, neuroendocrine, or medical disorder including renal insufficiency (CrCl<40 mL/min/1.73m2) Lifetime diagnosis of hypertension or diabetes or seizure disorder IQ<70 Acute risk for suicide and/or violence Pregnant lactating Current abuse of substances (alcohol, cocaine, stimulants, cannabis, opiates, sedative hypnotics) Current use or anticipated need for antipsychotics or mood stabilizers (all antipsychotics, also depakote, lithium, lamotrogine, pregabalin or any med with a mechanism of action like gabapentin), probenecid, selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors More than one previous gadolinium scan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, randomized, phase 1b, multiple dose trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POMA 40mg BID (80mg)<br>Subject will take 40mg pomaglumetad methionil (POMA) twice a day for 14 days. | Drug: Pomaglumetad methionil<br>* metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist<br>* Other names: POMA; LY2140023;|
| Experimental: POMA 80mg BID (160 mg)<br>Subject will take 80 mg pomaglumetad methionil (POMA) twice a day for 14 days | Drug: Pomaglumetad methionil<br>* metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist<br>* Other names: POMA; LY2140023;|
| Experimental: POMA 120mg BID (240mg)<br>Subject will take 120 mg pomaglumetad methionil (POMA) twice a day for 14 days | Drug: Pomaglumetad methionil<br>* metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist<br>* Other names: POMA; LY2140023;|
| Experimental: POMA 160 mg BID (320 mg)<br>Subject will take 160 mg pomaglumetad methionil (POMA) twice a day for 14 days | Drug: Pomaglumetad methionil<br>* metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist<br>* Other names: POMA; LY2140023;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14 | Effect of POMA on left CA1 CBV as measured by percent change from baseline scan (Time 1) to Day 14 scan (Time 2) | Baseline to 14 days of POMA/placebo |