Effects of GLYX-13 on Learning and Memory in Healthy Individuals and Those With Psychiatric Illness

Study Overview
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Brief Summary
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The present study proposes to evaluate the potential cognitive enhancing effects of GLYX-13, an NMDAR partial agonist, among a group of healthy adults and those with psychiatric illness on a series of functional magnetic resonance imaging (fMRI) learning and memory tasks.

Detailed Description
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In a single blind randomized parallel group design, we will evaluate the whether a single dose of GLYX-13 vs. placebo increases cognitive performance on tasks of learning, declarative memory, and working memory, and associated task-related increases in blood oxygen level-dependent (BOLD) activation in hippocampus and dorsolateral prefrontal cortex, respectively. Positive findings will provide biomarker evidence for GLYX-13 effects on neural systems underlying these cognitive processes.

Official Title
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Functional Neuroimaging Effects of the N-methyl-D-aspartate Receptor (NMDAR) Partial Agonist, GLYX-13, on Learning and Memory in Healthy Individuals

Conditions
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Psychiatric Illness, Healthy

Intervention / Treatment
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* Drug: GLYX-13
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all Individuals Male and female subjects Ages 18 - 40 years General intellectual abilities falling broadly within the average range (estimated intelligence quotient (IQ) between 80 - 119) Sufficient ability to understand study requirements and provide written informed consent For Patients -Diagnosis of Schizophrenia or Schizoaffective Disorder Exclusion Criteria: For all individuals: History of neurologic disorder or systemic medical condition that may interfere with central nervous system function History of seizures History of heard injury with loss of consciousness or concussion Positive screen for drugs of abuse: cocaine, marijuana, phencyclidine, ketamine, opioid, or other agent that is being abused in the opinion of the investigator Females who are currently pregnant or plan to become pregnant during the study period History of allergy, sensitivity, or intolerance to N-methyl-D-Aspartate receptor (NMDAR) ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone History of any ferromagnetic object in the body Presence of any medical device or implant for which MRI is contraindicated including cardiac pacemaker, aneurysm clip, cochlear implant, copper intrauterine device (IUD), neurostimulator, or any other device deemed unsafe Bullet or shrapnel in body Metallic braces or permanent retainer Significant claustrophobia For Healthy Individuals Personal history of any Axis I disorder according to the Structured Clinical Interview for the DSM-5 (SCID-5) criteria History of treatment with antidepressant, antipsychotic, stimulant,sedative/ hypnotic, mood stabilizing, or anticholinergic medications or lithium History among first-degree family members of any psychotic illness or major mood disorder (e.g., major depressive disorder, recurrent; bipolar I or II disorder) For Patients Treatment with Clozaril Change in medication within 1 month Hospitalization within 1 month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLYX-13<br>Single IV infusion of GLYX-13, 5mg/kg, | Drug: GLYX-13<br>* Single injection (5 mg/kg) of GLYX-13, an NMDAR partial agonist<br>|
| Placebo Comparator: Placebo<br>Single IV administration of placebo | Drug: Placebo<br>* Single injection of placebo (saline)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Change in fMRI BOLD Signal During a Category Learning Task | Evidence of enhanced functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal change during a category learning task among individuals receiving GLYX-13 administration compared to those receiving placebo. Value represents fMRI BOLD signal change (in % change) across a task derived functional network. Higher scores indicate greater task-based activation across this functional circuit. | within 1 hour of administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Category Learning Behavioral Performance | This measure reflects the percentage of correct trials on a category learning task in which subjects learned the category membership (group A or group B) of 8 three-digit numbers presented over 64 trials. Higher values (>50%) reflect increased accuracy in learning the category membership. | within 1 hour of administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy individuals, schizophrenia, schizoaffective disorder, learning, memory, cognitive enhancement, fMRI