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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: D-serine
* Behavioral: Cognitive Retraining (CRT)
* Drug: Placebo
* Behavioral: Cognitive Retraining Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia or schizoaffective disorder Exclusion Pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |