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Biomarkers in Schizophrenia

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
D Serine
Placebo
Sponsored by
Nathan Kline Institute for Psychiatric Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring biomarker, EEG, schizophrenia, NMDA, D-serine

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Nathan Kline Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

D-serine

Placebo

Arm Description

60 mg/kg/day

Outcomes

Primary Outcome Measures

PANSS Total
Positive and Negative Symptom Scale (PANSS) range 30-210
MMN Amplitude
Final MMN amplitude

Secondary Outcome Measures

MATRICS
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.
Visual P1

Full Information

First Posted
January 5, 2009
Last Updated
July 7, 2017
Sponsor
Nathan Kline Institute for Psychiatric Research
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1. Study Identification

Unique Protocol Identification Number
NCT00817336
Brief Title
Biomarkers in Schizophrenia
Official Title
Effect of an NMDA-based Intervention on Biomarker Measures of Cognitive Dysfunction in Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nathan Kline Institute for Psychiatric Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
biomarker, EEG, schizophrenia, NMDA, D-serine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
D-serine
Arm Type
Experimental
Arm Description
60 mg/kg/day
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
D Serine
Intervention Description
60 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
oral
Primary Outcome Measure Information:
Title
PANSS Total
Description
Positive and Negative Symptom Scale (PANSS) range 30-210
Time Frame
6 weeks
Title
MMN Amplitude
Description
Final MMN amplitude
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
MATRICS
Description
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.
Time Frame
6 weeks
Title
Visual P1
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel C Javitt, MD, PhD
Organizational Affiliation
New York University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nathan Kline Institute
City
Orangeburg
State/Province
New York
ZIP/Postal Code
10962
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28318835
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.
Results Reference
derived

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Biomarkers in Schizophrenia

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