Safety and Effectiveness of D-serine in Schizophrenia

Study Overview
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Brief Summary
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This study will determine whether increasing D-serine within the body will improve negative symptoms and cognitive impairments in people with schizophrenia.

Detailed Description
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Schizophrenia is a life-long brain disorder affecting approximately 1 percent of Americans each year. Schizophrenia can be extremely disabling, causing people to hear voices, experience paranoia or hallucinations, believe that others are controlling their thoughts, and even fail at maintaining a job or caring for themselves. Current medications help to relieve most of these symptoms, but not all. Some people with schizophrenia still suffer from negative symptoms, such as difficulty with talking, expressing emotions, and motivation; they may also suffer from cognitive impairments, such as decreased concentration and memory loss. D-serine, an amino acid found within the body, activates brain cell receptors that appear to play a role in learning and memory. This study will determine whether adding a D-serine solution to a stable antipsychotic medication regimen will decrease negative symptoms in people with schizophrenia. Participants in this open-label study will remain on their regular medication regimen for at least 2 weeks. During this time and before starting treatment, participants will be interviewed about their emotional problems, marital status, education, family background, employment history, and any drug or alcohol problems. Participants will also undergo a physical exam, an electrocardiogram (EKG), vital sign measurements, psychological tests, cognitive tasks, and an electroencephalogram (EEG). Participants will then begin 4 weeks of treatment with D-serine. In addition to participants' regular medication regimen, they will drink a D-serine powder mixed with water twice daily. Every 2 weeks, participants will undergo a physical exam and an interview about any changes in symptoms or emotional problems that they may be experiencing. Blood and urine samples will be taken throughout the study. After 4 weeks, participants will undergo an EKG, EEG, and the same psychological tests and cognitive tasks completed prior to treatment. A follow-up visit will occur 2 weeks post-treatment to monitor any changes in negative symptoms.

Official Title
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PK/PD Study of Escalating Dose D-serine as Adjunctive Treatment in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: D-serine
* Drug: D-serine
* Drug: D-serine
* Drug: D-serine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Structured Clinical Interview for DSM-III-R diagnosis of schizophrenia or schizoaffective disorder PANSS 3 factor negative symptom inclusion score greater than 20 prior to study entry PANSS total score between 60 and 110 Simpson-Angus Scale total score of 12 or less Calgary Depression Inventory total score of 10 and suicide score less than 2 No change in Clinical Global Impressions (CGI) Scale score prior to study entry Chlorpromazine (CPZ) equivalent of 1500 or less Willing to use an effective form of birth control throughout the study if sexually active Exclusion Criteria: High extrapyramidal symptom (EPS) levels Began, discontinued, or adjusted psychotropic medication within 2 weeks of study entry Taking investigational medication within 2 weeks of study entry Contraindication to study medication Serious or unstable medical illness Pregnant or breastfeeding Alcohol or drug abuse within 6 months of study entry Diagnosed with neurodegenerative disease or a seizure disorder History of a kidney impairment Currently taking clozapine Currently taking more than two antipsychotic medications Currently taking stimulants or cholinesterase inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D-serine 30 mg/kg<br>D-serine 30 mg/kg | Drug: D-serine<br>* D-serine at following dose levels: 30 mg/kg, 60 mg/kg, and 120 mg/kg. PK/PD studies done at day 1. Medication will be administered as powder dissolved in liquid given in two divided doses daily for 4 weeks.<br>Drug: D-serine<br> <br> |
| Experimental: D-serine 60 mg/kg<br>D-serine 60 mg/kg | Drug: D-serine<br>* D-serine at following dose levels: 30 mg/kg, 60 mg/kg, and 120 mg/kg. PK/PD studies done at day 1. Medication will be administered as powder dissolved in liquid given in two divided doses daily for 4 weeks.<br>Drug: D-serine<br> <br> |
| Experimental: D-serine 120 mg/kg<br>D-serine 120 mg/kg | Drug: D-serine<br>* D-serine at following dose levels: 30 mg/kg, 60 mg/kg, and 120 mg/kg. PK/PD studies done at day 1. Medication will be administered as powder dissolved in liquid given in two divided doses daily for 4 weeks.<br>Drug: D-serine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Safety Measures | number of renal adverse events (serum and urinalysis) | Measured at Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptoms Scale (PANSS) | Absolute Change in PANSS over four weeks (change between baseline and final measurements). The PANSS is a 30-item rating scale widely used in assessment of medication effects in schizophrenia. The PANSS ranges from 30-210, with lower scores showing less symptoms. Larger change is better. | Measured at Week 4 | 
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery | Change over 4 weeks. The MATRICS is a scale measuring cognition, and reported as T-score, with 50 as the population average and every 10 points representing a change of 1 standard deviation from the population average. Higher scores represent an improvement | Measured at Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Negative symptoms, NMDA, Glutamate, Glycine