Translational Neuroscience Optimization of GlyT1 Inhibitor (NCATS)

This is a Phase II, randomized, double-blind, placebo-controlled, cross-over POC study of stable patients with Schizophrenia or Schizoaffective disorder. The primary objective of this study is to test the efficacy of treatment with one of two does of a glycine transporter inhibitor (GlyT1I) combined with cognitive remediation to enhavce cognitive function. Subjects will be randomized to one of two doses of the glycine transporter inhibitor (GlyT1I) and placebo twice daily in addition to their antipsychotic medication for 2 treatment periods, each lasting a minimum of 5 weeks. Treatment periods will be separated by a washout period lasting approximately 3 weeks.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairments Associated With Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: PF-03463275

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Connecticut Mental Health Center
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1) Males or females 21 to 65 years of age (inclusive).
• 2) Diagnosis of Schizophrenia or Schizoaffective Disorder
• 3) Able to provide written informed consent.
• 4) Only CYP2D6 extensive metabolizers.

Exclusion Criteria:

• 1) No ongoing acute medical issues
• 2) Clinically significant ECG abnormality
• 3) Blood donation within eight weeks of the start of the study
• 4) Current treatment with Clozapine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-03463275 Active Dose #1; Active dose between 40mg	Drug: PF-03463275
Experimental: PF-03463275 Active Dose #2; Active dose between 60mg	Drug: PF-03463275
Placebo Comparator: Placebo; Placebo- no active dose of PF-03463275.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)	To test the efficacy of PF-03463275 on cognitive test performance specifically, the MCCB composite score was used. The MCCB consists of 10 tests and provides standard scores and percentiles for each of seven cognitive domains and an overall composite score. Domains assessed include: speed of processing, attention/vigilance, working memory (verbal and visual), verbal learning, visual learning, reasoning and problem solving, and social cognition. The MCCB overall composite score is presented as a T-score. The range of T-scores is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better overall cognitive functioning.	Change from baseline in cognitive measures at approximately 5 weeks. Mean scores were calculated per time point for each arm.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alteration in Symptom Domain Scores and Event Related Potentials (ERPs) With PF-03463275	To determine whether PF-03463275 impacts symptom domain scores and visual event related potentials (ERPs), analogous to long-term potentiation (LTP) with PF-03463275 treatment. A more positive value reflects a better outcome - there is no established range to report. A Z-score of 0 indicates the mean score. A positive z-score indicates the mean is higher than average.	Change from Baseline at approximately 1 week

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: July 10, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (Estimate): July 30, 2013

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 1303011716; 4UH3TR000960-02 (U.S. NIH Grant/Contract)