D-Serine Treatment of Negative Symptoms and Cognitive Deficits in Schizophrenia

Phase 3

Completed

• Conditions: Schizoaffective Disorder; Schizophrenia
• Interventions: Drug: Placebo; Drug: D-serine; Behavioral: Cognitive Retraining (CRT); Behavioral: Cognitive Retraining Placebo

• Registration Number: NCT00237809
• Lead Sponsor: Yale University

Brief Summary

This study is based on the hypothesis that by increasing N-methyl-D-aspartic acid (NMDA) receptor function in the brain and thereby increasing the capacity of the brain to both form new connections and strengthen existing connections, schizophrenic patients may derive both greater and sustained benefit from cognitive retraining.

Detailed Description

Patients with schizophrenia or schizoaffective disorder who are currently receiving antipsychotic medication will be randomly assigned in a double-blind manner to receive either D-serine (30 mg/kg) or placebo in addition to cognitive rehabilitation or a non-interactive placebo for 12 weeks.

Study Timeline

• Study Start: 2002-09
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-10-07
• Study First Posted: 2005-10-12
• Primary Completion: 2010-12
• Study Completion: 2012-09
• Results First Submitted: 2016-08-22
• Status Verified: 2017-03
• Results First Submitted QC: 2017-03-30
• Last Update Submitted: 2017-03-30
• Results First Posted: 2017-05-10
• Last Update Posted: 2017-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

• Diagnosis of schizophrenia or schizoaffective disorder

Exclusion

• Pregnant or lactating

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Drug and CRT	Cognitive Retraining (CRT)	D-serine/cog rehab
Placebo Drug and Placebo CRT	Placebo	Placebo/control
Placebo Drug and CRT	Cognitive Retraining (CRT)	Placebo/cog rehab
Drug and control CRT	Cognitive Retraining Placebo	D-serine/control
Placebo Drug and Placebo CRT	Cognitive Retraining Placebo	Placebo/control
Placebo Drug and CRT	Placebo	Placebo/cog rehab
Drug and control CRT	D-serine	D-serine/control
Drug and CRT	D-serine	D-serine/cog rehab

Primary Outcome Measures

Name	Time	Method
Positive and Negative Syndrome Scale (PANSS)	12 weeks	The PANSS is a handscored instrument. It uses 25 PANSS items organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The PANSS is based on findings that schizophrenia comprises at least two distinct syndromes. The positive syndrome consists of productive symptoms, while the negative syndrome consists of deficit features. This distinction is useful when developing treatment plans because you can focus on the type of symptoms the patient is experiencing. It is also useful when studying the effects of medication (e.g., in clinical drug trials) because it allows you to determine which type of symptoms are being affected. PANSS Total score minimum = 30, maximum = 210. The greater the score, the greater the symptoms.
Wisconsin Card Sorting Test (WCST)	12 weeks	The WCST allows the clinician to speculate to the following "frontal" lobe functions: strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior toward achieving a goal, and modulating impulsive responding. The test can be administered to those from 6.5 years to 89 years of age.The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Can be interpreted as: the greater the percentage, the greater the measured ability.
Hopkins Verbal Learning Test	12 weeks	The Hopkins Verbal Learning Test is designed to assess verbal learning and memory (immediate recall, delayed recall, delayed recognition). The assessment takes approximately 5-10 minutes with a 25-minute delay to complete and 2 minutes to score. The greater the score, the greater the measured recall. The score ranges from 0 to 24.
Spatial Span- Total Score	12 weeks	The Spatial Span subtest of the Wechsler Memory Scale can be used as an indicator of working memory and visuospatial processing. An increase in severity of impairment results in a decrease in Spatial Span Total Score. The range is 1 to 28.

Secondary Outcome Measures

Name	Time	Method
Heinrichs-Carpenter Quality of Life Scale	12 weeks	The Heinrichs-Carpenter Quality of Life Scale is a testing device. It has a range of possible scores, 0-126 used to evaluate social functioning \& behavior in patients with schizophrenia-lower scores represent poorer mental health.
UCSD Performance-Based Skills Assessment (UPSA)	12 weeks	The UCSD Performance-Based Skills Assessment (UPSA) is a role-play test designed to evaluate a person's functional capacity in two selected areas of basic living skills. These areas include Finance and Communication. Subjects being tested utilize props to demonstrate how they perform everyday activities and are assessed on their actual performance. The higher the score, the better the performance of an individual. The scores range from 0 to 100.
Simpson-Angus Neurological Rating Scale	12 weeks	Simpson-Angus Scale (SAS) is a 10-item rating scale that has been used widely for assessment in both clinical practice and research settings. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The highest possible score is 40.

Trial Locations

Locations (2)

Connecticut Mental Health Center; 🇺🇸 New Haven, Connecticut, United States

VA Connecticut Healthcare System; 🇺🇸 West Haven, Connecticut, United States