Biomarkers in Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nathan Kline Institute for Psychiatric Research
ClinicalTrials.gov Identifier:
NCT00817336
First received: January 5, 2009
Last updated: October 24, 2012
Last verified: June 2011

January 5, 2009
October 24, 2012
June 2009
July 2011   (final data collection date for primary outcome measure)
Change in biomarkers (QEEG, Auditory P50/mismatch negativity (MMN)/N1, Auditory P300, Visual P1) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00817336 on ClinicalTrials.gov Archive Site
  • MATRICS [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • PANSS [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • CGI [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Finger Tapping Motor Sequence Task (MST) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Biomarkers in Schizophrenia
Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Schizoaffective Disorder
  • Drug: D Serine
    60 mg/kg/day
  • Drug: Placebo
    oral
  • Experimental: D-serine
    60 mg/kg/day
    Intervention: Drug: D Serine
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
July 2011
July 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 64 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00817336
08I/C19-0
Yes
Nathan Kline Institute for Psychiatric Research
Nathan Kline Institute for Psychiatric Research
Not Provided
Principal Investigator: Daniel C Javitt, MD, PhD New York University
Nathan Kline Institute for Psychiatric Research
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP