Translational Neuroscience Optimization of GlyT1 Inhibitor

Phase 2CompletedNCT01911676

Yale University71 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Cognitive Impairments Associated With Schizophrenia

Interventions

Eligibility

Sex: ALLMin age: 21 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (2)

Connecticut Mental Health Center

New Haven, Connecticut, United States

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Outcomes

Primary Outcomes

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.

Time frame: Change from baseline in cognitive measures at approximately 5 weeks. Mean scores were calculated per time point for each arm.

Secondary Outcomes

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.

Time frame: Change from Baseline at approximately 1 week