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
  Purpose

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 Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: D Serine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Nathan Kline Institute for Psychiatric Research:

Primary Outcome Measures:
  • Change in biomarkers (QEEG, Auditory P50/mismatch negativity (MMN)/N1, Auditory P300, Visual P1) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 16
Study Start Date: June 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: D-serine
60 mg/kg/day
Drug: D Serine
60 mg/kg/day
Placebo Comparator: Placebo Drug: Placebo
oral

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00817336

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

No publications provided

Responsible Party: Nathan Kline Institute for Psychiatric Research
ClinicalTrials.gov Identifier: NCT00817336     History of Changes
Other Study ID Numbers: 08I/C19-0
Study First Received: January 5, 2009
Last Updated: October 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Nathan Kline Institute for Psychiatric Research:
biomarker
EEG
schizophrenia
NMDA
D-serine

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on August 28, 2014