Safety and Effectiveness of D-Serine in Schizophrenia - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00322023

Purpose

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

Condition	Intervention	Phase
Schizophrenia	Drug: D-serine	Phase II

MedlinePlus related topics: Schizophrenia

Drug Information available for: Glycine Serine Glutamic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	PK/PD Study of Escalating Dose D-Serine as Adjunctive Treatment in Schizophrenia

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Renal safety measures (serum, UA) [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Positive and Negative Symptoms Scale (PANSS) [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
Clinical Global Impression (CGI) [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	March 2006
Estimated Study Completion Date:	June 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Participants will receive treatment with D-serine	Drug: D-serine 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.

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322023

Locations

United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06512
United States, New York
The Zucker Hillside Hospital
Glen Oaks, New York, United States, 11004
The Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York, United States, 10962

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Daniel C. Javitt, MD, PhD

Nathan Kline Institute

More Information

Responsible Party:	Nathan Kline Institute ( Daniel Javitt )
Study ID Numbers:	U01 MH074356, DATR A5-EPTD
Study First Received:	May 2, 2006
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00322023
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Mental Health (NIMH):

Negative symptoms
NMDA
Glutamate
Glycine

Study placed in the following topic categories:

Schizophrenia
Glycine
Mental Disorders
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on January 14, 2009