Clinical High Risk for Psychosis
Conditions
Brief summary
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
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).
Interventions
metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist
Sponsors
National Institute of Mental Health (NIMH)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Identity of medications will be blinded having every subject take an equal number of pills (using identical looking tables of placebo)
Intervention model description
Double-blind, randomized, phase 1b, multiple dose trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14 | Baseline to 14 days of POMA/placebo | Effect of POMA on left CA1 CBV as measured by percent change from baseline scan (Time 1) to Day 14 scan (Time 2) |
Countries
United States
Participant flow
Pre-assignment details
5 participants consented to the protocol and underwent screening procedures but were not randomized (did not receive study medication). Reasons for screen fail: 1-withdrew consent 1-unable to undergo scan 3-study was paused due to COVID-19 pandemic
Participants by arm
| Arm | Count |
|---|---|
| POMA 40mg BID (80mg) Subject will take 40mg pomaglumetad methionil (POMA) twice a day for 14 days.
Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist | 3 |
| POMA 80mg BID (160 mg) Subject will take 80 mg pomaglumetad methionil (POMA) twice a day for 14 days
Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist | 3 |
| POMA 120mg BID (240mg) Subject will take 120 mg pomaglumetad methionil (POMA) twice a day for 14 days
Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist | 2 |
| POMA 160 mg BID (320 mg) Subject will take 160 mg pomaglumetad methionil (POMA) twice a day for 14 days
Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist | 3 |
| Total | 11 |
Baseline characteristics
| Characteristic | POMA 40mg BID (80mg) | POMA 80mg BID (160 mg) | POMA 120mg BID (240mg) | POMA 160 mg BID (320 mg) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 3 |
| other Total, other adverse events | 1 / 3 | 3 / 3 | 1 / 2 | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 3 |
Outcome results
Primary
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)
Time frame: Baseline to 14 days of POMA/placebo
Population: participants who completed both baseline and Day 14 scans
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| POMA 40mg BID (80mg) | Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14 | 0.40684405 Percent change | Standard Deviation 0.63605395 |
| POMA 80mg BID (160 mg) | Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14 | -0.081559 Percent change | Standard Deviation 0.1522939 |
| POMA 120mg BID (240mg) | Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14 | 0.0219668 Percent change | Standard Deviation 0.1484273 |
| POMA 160 mg BID (320 mg) | Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14 | -0.0269017 Percent change | Standard Deviation 0 |