Biomarkers in Schizophrenia

Schizophrenia Clinical Trial

Official title:

Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00817336
• Other study ID #: 08I/C19-0
• Status: Completed
• Phase: Phase 2
• First received: January 5, 2009
• Last updated: April 15, 2015
• Start date: June 2009
• Est. completion date: July 2011

Study information

• Verified date: June 2011
• Source: Nathan Kline Institute for Psychiatric Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• D Serine
60 mg/kg/day
• Placebo
oral

Locations

Country	Name	City	State
United States	Nathan Kline Institute	Orangeburg	New York

Sponsors (1)

Lead Sponsor	Collaborator
Nathan Kline Institute for Psychiatric Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in biomarkers (QEEG, Auditory P50/mismatch negativity (MMN)/N1, Auditory P300, Visual P1)		6 weeks	No
Secondary	MATRICS		6 weeks	No
Secondary	PANSS		6 weeks	No
Secondary	CGI		6 weeks	No