Clinical trial NCT00817336: Biomarkers in Schizophrenia
Official title: Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: biomarker
EEG
schizophrenia
NMDA
D-serine
Lead sponsor: Nathan Kline Institute for Psychiatric Research
Sponsor class: OTHER
First posted: 2009-01-06
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: PANSS Total
timeFrame: 6 weeks
measure: MMN Amplitude
timeFrame: 6 weeks
Secondary outcomes:
measure: MATRICS
timeFrame: 6 weeks
measure: Visual P1
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Orangeburg
country: United States
facility: Nathan Kline Institute
state: New York
Study officials:
affiliation: New York University
name: Daniel C Javitt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kantrowitz JT, Epstein ML, Lee M, Lehrfeld N, Nolan KA, Shope C, Petkova E, Silipo G, Javitt DC. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res. 2018 Jan;191:70-79. doi: 10.1016/j.schres.2017.02.027. Epub 2017 Mar 18.