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

• ClinicalTrials.gov Identifier: NCT00237809
• Recruitment Status: Completed
• First Posted: October 12, 2005
• Results First Posted: May 10, 2017
• Last Update Posted: May 10, 2017
• Sponsor: Yale University
• Collaborators: National Alliance for Research on Schizophrenia and Depression; Donaghue Medical Research Foundation
• Information provided by (Responsible Party): Deepak C. D'Souza, Yale University

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
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: September 2012

Arms and Interventions

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	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

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

Criteria

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder

Exclusion

• Pregnant or lactating

Contacts and Locations

Locations

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

Investigators

• Principal Investigator: Deepak C D'Souza, M.D.; Yale University

More Information

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.

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.

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.

• Responsible Party: Deepak C. D'Souza, Associate Professor, Yale University
• ClinicalTrials.gov Identifier: NCT00237809
• Other Study ID Numbers: 23594; DF01-015
• First Posted: October 12, 2005
• Results First Posted: May 10, 2017
• Last Update Posted: May 10, 2017
• Last Verified: March 2017

Additional relevant MeSH terms:

Schizophrenia; Psychotic Disorders; Cognition Disorders; Cognitive Dysfunction; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurocognitive Disorders