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

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ClinicalTrials.gov Identifier: NCT00237809
Recruitment Status : Completed
First Posted : October 12, 2005
Results First Posted : May 10, 2017
Last Update Posted : May 10, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Drug: D-serine Behavioral: Cognitive Retraining (CRT) Drug: Placebo Behavioral: Cognitive Retraining Placebo Phase 3

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: D-Serine Treatment of Negative Symptoms and Cognitive Deficits in Schizophrenia
Study Start Date : September 2002
Primary Completion Date : December 2010
Study Completion Date : September 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Serine
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Drug and control CRT
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
Drug: Placebo
Placebo D-serine Drug
Behavioral: Cognitive Retraining Placebo
Cognitive retraining therapy (CRT) control
Experimental: Placebo Drug and CRT
Placebo/cog rehab
Behavioral: Cognitive Retraining (CRT)
Cognitive retraining therapy (CRT)
Drug: Placebo
Placebo D-serine Drug

Outcome Measures

Primary Outcome Measures :
  1. Wisconsin Card Sorting Test (WCST) [ Time Frame: 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.

  2. Hopkins Verbal Learning Test [ Time Frame: 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.

  3. Spatial Span- Total Score [ Time Frame: 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.

  4. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 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.

Secondary Outcome Measures :
  1. Heinrichs-Carpenter Quality of Life Scale [ Time Frame: 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.

  2. Simpson-Angus Neurological Rating Scale [ Time Frame: 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.

  3. UCSD Performance-Based Skills Assessment (UPSA) [ Time Frame: 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.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of schizophrenia or schizoaffective disorder


  • Pregnant or lactating
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00237809

United States, Connecticut
Connecticut Mental Health Center
New Haven, Connecticut, United States, 06508
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
National Alliance for Research on Schizophrenia and Depression
Donaghue Medical Research Foundation
Principal Investigator: Deepak C D'Souza, M.D. Yale University
More Information

Responsible Party: Deepak C. D'Souza, Associate Professor, Yale University
ClinicalTrials.gov Identifier: NCT00237809     History of Changes
Other Study ID Numbers: 23594
First Posted: October 12, 2005    Key Record Dates
Results First Posted: May 10, 2017
Last Update Posted: May 10, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Psychotic Disorders
Cognition Disorders
Cognitive Dysfunction
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Neurocognitive Disorders