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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Drug: D-serine; Behavioral: Cognitive Retraining Placebo; Behavioral: Cognitive Retraining (CRT); Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06508
      • Connecticut Mental Health Center
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder

Exclusion

• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug and control CRT; D-serine/control	Drug: D-serine; D-serine (30 mg/kg); Behavioral: Cognitive Retraining Placebo; Cognitive retraining therapy (CRT) control
Experimental: Drug and CRT; D-serine/cog rehab	Drug: D-serine; D-serine (30 mg/kg); Behavioral: Cognitive Retraining (CRT); Cognitive retraining therapy (CRT)
Experimental: Placebo Drug and Placebo CRT; Placebo/control	Behavioral: Cognitive Retraining Placebo; Cognitive retraining therapy (CRT) control; Drug: Placebo; Placebo D-serine Drug
Experimental: Placebo Drug and CRT; Placebo/cog rehab	Behavioral: Cognitive Retraining (CRT); Cognitive retraining therapy (CRT); Drug: Placebo; Placebo D-serine Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wisconsin Card Sorting Test (WCST)	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.	12 weeks
Hopkins Verbal Learning Test	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.	12 weeks
Spatial Span- Total Score	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.	12 weeks
Positive and Negative Syndrome Scale (PANSS)	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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heinrichs-Carpenter Quality of Life Scale	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.	12 weeks
Simpson-Angus Neurological Rating Scale	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.	12 weeks
UCSD Performance-Based Skills Assessment (UPSA)	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.	12 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Alliance for Research on Schizophrenia and Depression; Donaghue Medical Research Foundation

Publications and helpful links

General Publications

• Tsai GE, Yang P, Chung LC, Tsai IC, Tsai CW, Coyle JT. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry. 1999 Nov;156(11):1822-5. doi: 10.1176/ajp.156.11.1822.
• Tsai G, Yang P, Chung LC, Lange N, Coyle JT. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998 Dec 1;44(11):1081-9. doi: 10.1016/s0006-3223(98)00279-0.
• Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, Catinari S, Ermilov M. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. 2005 Mar 15;57(6):577-85. doi: 10.1016/j.biopsych.2004.12.037.

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: October 7, 2005
• First Posted (Estimate): October 12, 2005

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: March 30, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Cognitive Dysfunction; Cognition Disorders
• Other Study ID Numbers: 23594; DF01-015