Glutamate Reducing Interventions in Schizophrenia

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT03321617
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 16
• Location: 1
• Arms: 4
• Actual Duration (Months): 22.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Clinical High Risk for Psychosis	Drug: Pomaglumetad methionil	Phase 1

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double-blind, randomized, phase 1b, multiple dose trialDouble-blind, randomized, phase 1b, multiple dose trial
• Masking: Triple (Participant, 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)
• Primary Purpose: Treatment
• Official Title: Glutamate Reducing Interventions in Schizophrenia
• Actual Study Start Date: Apr 17, 2018
• Actual Primary Completion Date: Mar 13, 2020
• Actual Study Completion Date: Mar 13, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Scott Small, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol - Aug 24, 2020
• Statistical Analysis Plan - Sep 2, 2021
• Informed Consent Form - Aug 24, 2020

More Information

Publications

None provided.

• Responsible Party: Scott Small, Clinical Psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT03321617
• Other Study ID Numbers: 7459; R61MH112800-01
• First Posted: Oct 25, 2017
• Last Update Posted: Dec 1, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Schizophrenia

Study Results

Participant Flow

Pre-assignment Detail	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

Arm/Group Title	POMA 40mg BID (80mg)	POMA 80mg BID (160 mg)	POMA 120mg BID (240mg)	POMA 160 mg BID (320 mg)
Arm/Group Description	Subject will take 40mg pomaglumetad methionil (POMA) twice a day for 14 days. Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 80 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 120 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 160 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist
Period Title: Overall Study
STARTED	3	3	2	3
COMPLETED	2	3	2	2
NOT COMPLETED	1	0	0	1

Baseline Characteristics

Arm/Group Title	POMA 40mg BID (80mg)	POMA 80mg BID (160 mg)	POMA 120mg BID (240mg)	POMA 160 mg BID (320 mg)	Total
Arm/Group Description	Subject will take 40mg pomaglumetad methionil (POMA) twice a day for 14 days. Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 80 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 120 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 160 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Total of all reporting groups
Overall Participants	3	3	2	3	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	3 100%	2 100%	3 100%	11 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	2 66.7%	0 0%	2 66.7%	4 36.4%
Male	3 100%	1 33.3%	2 100%	1 33.3%	7 63.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 66.7%	0 0%	0 0%	1 33.3%	3 27.3%
Not Hispanic or Latino	1 33.3%	3 100%	2 100%	2 66.7%	8 72.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 66.7%	2 100%	1 33.3%	5 45.5%
White	2 66.7%	1 33.3%	0 0%	1 33.3%	4 36.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 33.3%	0 0%	0 0%	1 33.3%	2 18.2%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Left Hippocampal CA1 Region Cerebral Blood Volume (CBV) From Baseline to Day 14
Description	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

Outcome Measure Data

Analysis Population Description

participants who completed both baseline and Day 14 scans

Arm/Group Title	POMA 40mg BID (80mg)	POMA 80mg BID (160 mg)	POMA 120mg BID (240mg)	POMA 160 mg BID (320 mg)
Arm/Group Description	Subject will take 40mg pomaglumetad methionil (POMA) twice a day for 14 days. Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 80 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 120 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist	Subject will take 160 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist
Measure Participants	2	3	2	2
Mean (Standard Deviation) [Percent change]	0.40684405 (.63605395)	-0.081559 (0.1522939)	0.0219668 (0.1484273)	-0.0269017 (0)

Adverse Events

Time Frame	From consent to 30 days after last dose of study medication, up to 74 days (30-day screening period, 14-day randomization period, 30 day follow up)
Arm/Group Title	POMA 40mg BID (80mg)		POMA 80mg BID (160 mg)		POMA 120mg BID (240mg)		POMA 160 mg BID (320 mg)
Arm/Group Description	Subject will take 40mg pomaglumetad methionil (POMA) twice a day for 14 days. Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist		Subject will take 80 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist		Subject will take 120 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist		Subject will take 160 mg pomaglumetad methionil (POMA) twice a day for 14 days Pomaglumetad methionil: metabotropic glutamate 2/3 receptor (mGlu2/3R) agonist
All Cause Mortality
	POMA 40mg BID (80mg)		POMA 80mg BID (160 mg)		POMA 120mg BID (240mg)		POMA 160 mg BID (320 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/2 (0%)		0/3 (0%)
Serious Adverse Events
	POMA 40mg BID (80mg)		POMA 80mg BID (160 mg)		POMA 120mg BID (240mg)		POMA 160 mg BID (320 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/2 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	POMA 40mg BID (80mg)		POMA 80mg BID (160 mg)		POMA 120mg BID (240mg)		POMA 160 mg BID (320 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		3/3 (100%)		1/2 (50%)		2/3 (66.7%)
Gastrointestinal disorders
nausea	1/3 (33.3%)	1	2/3 (66.7%)	2	1/2 (50%)	1	2/3 (66.7%)	2
General disorders
itching/restlessness	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/3 (0%)	0
Nervous system disorders
lightheadedness	0/3 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/3 (33.3%)	1
dizziness	0/3 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/3 (33.3%)	1
sedation	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.