Healthy, Psychiatric Illness
Conditions
Keywords
healthy individuals, schizophrenia, schizoaffective disorder, learning, memory, cognitive enhancement, fMRI
Brief summary
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
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.
Interventions
DRUGGLYX-13
Single injection (5 mg/kg) of GLYX-13, an NMDAR partial agonist
DRUGPlacebo
Single injection of placebo (saline)
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Change in fMRI BOLD Signal During a Category Learning Task | within 1 hour of administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Category Learning Behavioral Performance | within 1 hour of administration | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GLYX-13 Single IV infusion of GLYX-13, 5mg/kg,
GLYX-13: Single injection (5 mg/kg) of GLYX-13, an NMDAR partial agonist | 21 |
| Placebo Single IV administration of placebo
Placebo: Single injection of placebo (saline) | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Excessive motion in MRI resulted in discontinuation. | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | GLYX-13 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 21 Participants | 42 Participants |
| Age, Continuous | 27.2 years STANDARD_DEVIATION 4.5 | 25.2 years STANDARD_DEVIATION 5 | 26.2 years STANDARD_DEVIATION 4.8 |
| Estimated Intelligence Quotient (IQ) | 105.7 units on a scale STANDARD_DEVIATION 9.2 | 107.9 units on a scale STANDARD_DEVIATION 8.8 | 106.8 units on a scale STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 13 Participants | 27 Participants |
| Region of Enrollment United States | 21 participants | 21 participants | 42 participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 9 / 21 | 9 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
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.
Time frame: within 1 hour of administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLYX-13 | Percentage of Change in fMRI BOLD Signal During a Category Learning Task | .16 percentage of BOLD signal change | Standard Deviation 0.16 |
| Placebo | Percentage of Change in fMRI BOLD Signal During a Category Learning Task | .08 percentage of BOLD signal change | Standard Deviation 0.15 |
Comparison: Change in BOLD signal activation across task derived learning circuit were compared between GLYX-13 and placebo groups using an independent group t-test.p-value: 0.1t-test, 2 sided
Secondary
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.
Time frame: within 1 hour of administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLYX-13 | Category Learning Behavioral Performance | 72.5 percentage of correct trials | Standard Deviation 16.4 |
| Placebo | Category Learning Behavioral Performance | 75.2 percentage of correct trials | Standard Deviation 14 |
p-value: 0.57t-test, 2 sided