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

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

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.

Study Overview

• Status: Terminated
• Conditions: Healthy; Psychiatric Illness
• Intervention / Treatment: Drug: GLYX-13; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: James L Reilly, PhD, Northwestern University

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: April 29, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (Estimate): May 1, 2013

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: memory; schizophrenia; schizoaffective disorder; fMRI; learning; cognitive enhancement; healthy individuals
• Additional Relevant MeSH Terms: Mental Disorders
• Other Study ID Numbers: STU77430