Biomarkers in Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00817336
Recruitment Status : Completed
First Posted : January 6, 2009
Results First Posted : August 2, 2017
Last Update Posted : August 2, 2017
Information provided by (Responsible Party):
Nathan Kline Institute for Psychiatric Research

Brief Summary:
N-methyl-D-aspartate (NMDA)-type glutamate receptors are thought to play a pivotal role in neurocognitive dysfunction associated with schizophrenia. Further, several novel glutamate-based classes of compound are presently in development as potential novel treatments for persistent negative and cognitive symptoms. The study will assess effectiveness of a NMDA-based intervention on biomarkers related to schizophrenia as a mechanism for developing appropriate outcome batteries for future trials of novel compounds.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Drug: D Serine Drug: Placebo Phase 2

Detailed Description:
16 in- or outpatients with DSM-IV-TR schizophrenia or schizoaffective disorder and prominent negative symptoms will be recruited for this study. This study will consist of a randomized trial of D-serine (60 mg/kg/d) vs. placebo using a crossover design with a 2-week baseline lead-in, and two 6-week intervention arms separated by a two week, placebo controlled washout period. Biomarkers will be assessed at baseline for each treatment arm, acutely (day 7) following treatment initiation, and following 6 weeks of treatment (6 biomarker sessions total). Primary biomarker outcome measures will include 1) amplitude of the mismatch negativity (MMN) waveform and 2) amplitude of the visual P1 potential. Symptomatic outcome measures will include PANSS and composite score of the MATRICS neuropsychological battery. The study will be supported from ongoing NIMH-funded Cooperative Drug Development Grant (CDDG) to the PI.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia
Study Start Date : June 2009
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: D-serine
60 mg/kg/day
Drug: D Serine
60 mg/kg/day
Placebo Comparator: Placebo Drug: Placebo

Primary Outcome Measures :
  1. PANSS Total [ Time Frame: 6 weeks ]
    Positive and Negative Symptom Scale (PANSS) range 30-210

  2. MMN Amplitude [ Time Frame: 6 weeks ]
    Final MMN amplitude

Secondary Outcome Measures :
  1. MATRICS [ Time Frame: 6 weeks ]
    MATRICS assessing 7 domains (Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition. Raw scores are converted into a composite T-score (normative mean = 50; standard deviation = 10), where higher values indicated less impairment.

  2. Visual P1 [ Time Frame: 6 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Age 18-64
  • SCID diagnosis of Schizophrenia or Schizoaffective Disorder.
  • PANSS 3 factor negative symptom (screening and baseline visit 1 and visit 3) score of >20 and PANSS total score between 60-110. Any degree of positive symptoms is acceptable but the total PANSS score must not exceed 110.
  • SAS total score less than or equal to 12 and a Calgary Depression Inventory total score less than or equal to 10 and suicide (item 8) less than moderate (<2).
  • Two consecutive CGI ratings at screening and baseline (visit 1 and 3) with no change in score.
  • Estimated Glomerular Filtration Rate (GFR)(a measure of renal function) greater than or equal to 60.

Exclusion criteria:

  • Organic brain disorder, including epilepsy; mental retardation; or a medical condition whose pathology or treatment would likely alter the presentation or treatment of schizophrenia or significantly increase the risk associated with any of the proposed treatments
  • Current DSM-IV diagnosis of drug/alcohol abuse in last month and current DSM-IV diagnosis of drug/alcohol dependence in last 6 months
  • Pregnant female patients
  • Impaired renal function
  • Significant extrapyramidal symptoms (as reflected by a total score of 10 or above on the SAS scale), and depressive symptoms (as reflected by a score of 10 or above on the Calgary Depression Scale for Schizophrenia)
  • Patients who are unable to or unwilling to participate in the Cognitive assessment (MATRICS) and the electrophysiology tasks .
  • Patients on clozapine

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 identifier (NCT number): NCT00817336

United States, New York
Nathan Kline Institute
Orangeburg, New York, United States, 10962
Sponsors and Collaborators
Nathan Kline Institute for Psychiatric Research
Principal Investigator: Daniel C Javitt, MD, PhD New York University

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Nathan Kline Institute for Psychiatric Research Identifier: NCT00817336     History of Changes
Other Study ID Numbers: 08I/C19-0
First Posted: January 6, 2009    Key Record Dates
Results First Posted: August 2, 2017
Last Update Posted: August 2, 2017
Last Verified: July 2017

Keywords provided by Nathan Kline Institute for Psychiatric Research:

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders