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Event-Related Potential (ERP) Biomarkers in Subjects With Schizophrenia and Healthy Volunteer Subjects

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ClinicalTrials.gov Identifier: NCT04025502
Recruitment Status : Completed
First Posted : July 19, 2019
Last Update Posted : February 24, 2021
Sponsor:
Collaborators:
Novartis
Alkermes, Inc.
Anavex Life Sciences Corp.
Merck Sharp & Dohme Corp.
Takeda
Sage Therapeutics
H. Lundbeck A/S
Astellas Pharma Inc
Apex Innovative Sciences
Columbia University
COGNISION
Information provided by (Responsible Party):
ERP Biomarker Qualification Consortium

Tracking Information
First Submitted Date June 23, 2019
First Posted Date July 19, 2019
Last Update Posted Date February 24, 2021
Actual Study Start Date October 7, 2019
Actual Primary Completion Date December 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 19, 2019)
  • Amplitude (in microvolts) for parameters from the ERP tests. [ Time Frame: 12-18 months ]
    Amplitude (in microvolts) for the following parameters from the ERP tests will be collected as primary endpoints:
    1. Passive, Tone-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    2. Passive, Duration-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    3. Active, Auditory Oddball ERP
      • N100
      • P3b
  • Latency (in milliseconds) for parameters from the ERP tests. [ Time Frame: 12-18 months ]
    Latency (in milliseconds) for the following parameters from the ERP tests will be collected as primary endpoints:
    1. Passive, Tone-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    2. Passive, Duration-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    3. Active, Auditory Oddball ERP
      • N100
      • P3b
  • Task accuracy from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: 12-18 months ]
    Task accuracy as a percentage of correct behavioral responses during the active, auditory oddball ERP test will be collected as a primary endpoint.
  • Reaction time from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: 12-18 months ]
    Reaction time for the correct behavioral responses to the test measured in milliseconds will be collected as a primary endpoint during the active, auditory oddball ERP test.
  • Total Power from the auditory steady-state response (ASSR) paradigm. [ Time Frame: 12-18 months ]
    Total Power (measured in µv2/Hz) will be collected during the ASSR paradigm as a primary endpoint.
  • Inter-trial coherence (ITC) from the auditory steady-state response (ASSR) paradigm. [ Time Frame: 12-18 months ]
    Inter-trial coherence (ITC) measured on a scale between 0 (no coherence) and 1 (maximum coherence) will be collected during the ASSR paradigm as a primary endpoint.
  • Absolute Power for Pharmaco-EEG parameters per IPEG guidelines. [ Time Frame: 12-18 months ]
    Absolute Power (measured in µv2/Hz) will be collected from the Resting State EEG as a primary endpoint for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
    • Gamma power
  • Relative Power for Pharmaco-EEG parameters per IPEG guidelines. [ Time Frame: 12-18 months ]
    Relative Power measured on a scale from 0 (no power in frequency band) to 1 (all EEG power in that frequency band) will be collected from the Resting State EEG as a primary endpoint for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
  • Dominant frequency in the Alpha frequency band per IPEG guidelines [ Time Frame: 12-18 months ]
    Dominant frequency measured in Hz in the frequency interval between 6.0 and < 12.5 Hz will be collected from the Resting State EEG as a primary endpoint.
  • Theta/Beta ratio and Slow Wave index per IPEG guidelines. [ Time Frame: 12-18 months ]
    Theta/Beta ratio and Slow Wave index (Alpha/Delta+Theta) measured in percentage will be collected from the Resting State EEG as primary endpoints.
  • Functional assessments as derived from the Brief Assessment of Cognition in Schizophrenia (BACS). [ Time Frame: 12-18 months ]
    The following parameters will be collected for the BACS: BACS Variable Ranges Description Range Low Range High Unit Verbal Memory Total Score 0 75 n/a Digit Sequencing 0 28 n/a Token Motor Total Correct 0 100 n/a Verbal Fluency Total 0 100 n/a Symbol Coding 0 110 n/a Tower of London 0 22 n/a Verbal Memory T-Score -100 100 n/a Digit Sequencing T-Score -100 100 n/a Token Motor T-Score -100 100 n/a Verbal Fluency T-Score -100 100 n/a Symbol Coding T-Score -100 100 n/a Tower of London T-Score -100 100 n/a
  • Functional assessments as derived from the Positive and Negative Symptom Scale for Schizophrenia (PANSS). [ Time Frame: 12-18 months ]
    The PANSS items are divided into three sections: Positive symptoms, negative symptoms, and general symptoms. The following parameters will be collected: PANSS Variable Ranges Description Range Low Range High Unit PANSS Items 1-30 1 7 n/a PANSS Total Score 30 210 n/a
  • Functional assessments as derived from the Virtual Reality Functional Capacity Assessment Tool (VRFCAT). [ Time Frame: 12-18 months ]
    The following parameters for the VRFCAT will be collected: VRFCAT Variable Ranges Description Range Low Range High Unit VRFCAT- Adjusted Total Time 0 60000 msec VRFCAT- Total Error Count 0 60 n/a VRFCAT- Total Forced Progressions 0 12 n/a Adjusted Total Time T-Score -100 100 n/a Total Errors T-Score -100 100 n/a Total Forced Progressions T-Score -100 100 n/a
Original Primary Outcome Measures
 (submitted: July 16, 2019)
  • Amplitude (in microvolts) for parameters from the ERP tests. [ Time Frame: 12-18 months ]
    Amplitude (in microvolts) for the following parameters from the ERP tests will be collected as primary endpoints:
    1. Passive, Tone-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    2. Passive, Duration-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    3. Active, Auditory Oddball ERP
      • N100
      • P3b
  • Latency (in milliseconds) for parameters from the ERP tests. [ Time Frame: 12-18 months ]
    Latency (in milliseconds) for the following parameters from the ERP tests will be collected as primary endpoints:
    1. Passive, Tone-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    2. Passive, Duration-deviant, Auditory Oddball ERP
      • N100
      • MMN
      • P3a
    3. Active, Auditory Oddball ERP
      • N100
      • P3b
  • Task accuracy from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: 12-18 months ]
    Task accuracy as a percentage of correct behavioral responses during the active, auditory oddball ERP test will be collected as a primary endpoint.
  • Reaction time from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: 12-18 months ]
    Reaction time for the correct behavioral responses to the test measured in milliseconds will be collected as a primary endpoint during the active, auditory oddball ERP test.
  • Total Power from the auditory steady-state response (ASSR) paradigm. [ Time Frame: 12-18 months ]
    Total Power (measured in µv2/Hz) will be collected during the ASSR paradigm as a primary endpoint.
  • Inter-trial coherence (ITC) from the auditory steady-state response (ASSR) paradigm. [ Time Frame: 12-18 months ]
    Inter-trial coherence (ITC) measured on a scale between 0 (no coherence) and 1 (maximum coherence) will be collected during the ASSR paradigm as a primary endpoint.
  • Absolute Power for Pharmaco-EEG parameters per IPEG guidelines. [ Time Frame: 12-18 months ]
    Absolute Power (measured in µv2/Hz) will be collected from the Resting State EEG as a primary endpoint for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
    • Gamma power
  • Relative Power for Pharmaco-EEG parameters per IPEG guidelines. [ Time Frame: 12-18 months ]
    Relative Power measured on a scale from 0 (no power in frequency band) to 1 (all EEG power in that frequency band) will be collected from the Resting State EEG as a primary endpoint for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
  • Dominant frequency in the Alpha frequency band per IPEG guidelines [ Time Frame: 12-18 months ]
    Dominant frequency measured in Hz in the frequency interval between 6.0 and < 12.5 Hz will be collected from the Resting State EEG as a primary endpoint.
  • Theta/Beta ratio and Slow Wave index per IPEG guidelines. [ Time Frame: 12-18 months ]
    Theta/Beta ratio and Slow Wave index (Alpha/Delta+Theta) measured in percentage will be collected from the Resting State EEG as primary endpoints.
  • Functional assessments as derived from the Brief Assessment of Cognition in Schizophrenia (BACS). [ Time Frame: 12-18 months ]
    The score for the BACS test will be collected as a primary endpoint.
  • Functional assessments as derived from the Positive and Negative Symptom Scale for Schizophrenia (PANSS). [ Time Frame: 12-18 months ]
    The score for the PANSS test (minimum 30, maximum 210) will be collected as a primary endpoint.
  • Functional assessments as derived from the Virtual Reality Functional Capacity Assessment Tool (VRFCAT). [ Time Frame: 12-18 months ]
    The score for the VRFCAT test will be collected as a primary endpoint.
Change History
Current Secondary Outcome Measures
 (submitted: July 16, 2019)
Correlations between EEG/ERP measures and psychometric measures in Schizophrenia subjects. [ Time Frame: 12-18 months ]
Pearson Correlation coefficients between EEG/ERP measures and scores from the functional assessments (BACS, PANSS, and VRFCAT) will be collected as secondary outcome measures.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Event-Related Potential (ERP) Biomarkers in Subjects With Schizophrenia and Healthy Volunteer Subjects
Official Title A Multi-Center Study of Event-Related Potential (ERP) Biomarkers in Subjects With Schizophrenia and Healthy Volunteer Subjects
Brief Summary This is an observational, non-interventional study that will recruit Healthy Volunteers (HV) and subjects with clinically confirmed Schizophrenia (SZ). The purpose of this study is to establish the mean and variance across the HV and SZ cohorts, sites, and repeated tests of the electroencephalogram(EEG)/Event-related potentials (ERP) measures.
Detailed Description

Among the most replicated pathophysiological findings in schizophrenia is the impairment of Event-Related Potentials (ERPs) recorded during the auditory oddball procedure. In this procedure, time-locked electroencephalogram (EEG) responses are recorded during auditory processing of frequent and rare tones differing in pitch or duration. In addition, a smaller but substantial literature has reported deficits in the auditory steady-state EEG response (ASSR) to a 40 Hz train of auditory tones in subjects with schizophrenia versus healthy control subjects.

While measurement of ERPs in the drug development setting has shown promise, the instruments, infrastructure, and standardization of these methods has lagged. New, portable, easy-to-use, Food and Drug Administration (FDA)-approved devices are now available for the automated collection and analysis of EEG and ERP data.

This observational, non-interventional, clinical study will recruit healthy volunteer subjects (HV) and subjects with clinically confirmed schizophrenia (SZ), and will establish the mean and variance across HV and SZ cohorts, sites and repeated tests, of EEG and ERP measures collected with a standardized EEG/ERP device. The study will also examine the relationship between specific EEG/ERP features and measures of positive, negative, and cognitive symptoms and global function in SZ subjects.

The data collected in this study is intended to replicate published observations of the magnitude of deficit in ERPs in SZ versus HV subjects, and to support the design of subsequent interventional studies that will make use of ERPs. Furthermore, these data will be submitted to support qualification of the ERP biomarkers through the FDA Drug Development Tools Biomarker Qualification Program.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Saliva drug screen to rule out illicit drug use for all three visits (Screening visit, Baseline visit, and Retest visit).
Sampling Method Non-Probability Sample
Study Population

There will be four different sites where the participants will be selected in the following states: California, New Jersey, and New York.

Recruitment methods:

  • Database of individuals who have agreed to be contacted
  • Advertisements
  • Physician to physician referrals
Condition Schizophrenia
Intervention Device: Event-Related Potentials (ERP) and Electroencephalogram (EEG) testing with the COGNISION® System
The testing protocol consists of an auditory oddball Event-Related Potential (ERP) paradigm, 40Hz ASSR, and the collection of 6 minutes of resting electroencephalogram (EEG). During the ERP paradigm a variety of auditory stimuli are played through the system's earphones while voltage potentials are recorded from the subject's scalp. At the end of the ERP session, 6 minutes of EEG data will be recorded while the subject is resting. The entire procedure, including set up, instructions to the subject and actual test is expected to take 60-75 minutes.
Study Groups/Cohorts
  • Healthy Volunteer Subjects (HV)

    Male and female subjects 21-50 years of age, who are in good and stable health with no history or evidence of clinically relevant medical or neuropsychiatric illness.

    Healthy Volunteer Subjects will undergo Event-Related Potential (ERP)/electroencephalogram (EEG) testing with the COGNISION® System.

    Intervention: Device: Event-Related Potentials (ERP) and Electroencephalogram (EEG) testing with the COGNISION® System
  • Subjects with Schizophrenia (SZ)

    Otherwise healthy male and female subjects 21-50 years of age, who have a current diagnosis of Schizophrenia with a duration of illness greater than or equal to one year.

    Subjects with Schizophrenia (SZ) will undergo Event-Related Potential (ERP)/electroencephalogram (EEG) testing with the COGNISION® System.

    Intervention: Device: Event-Related Potentials (ERP) and Electroencephalogram (EEG) testing with the COGNISION® System
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: February 19, 2021)
161
Original Estimated Enrollment
 (submitted: July 16, 2019)
160
Actual Study Completion Date January 31, 2021
Actual Primary Completion Date December 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • Inclusion Criteria for Healthy Volunteer Subjects (HV)

    • Healthy male and female subjects 21-50 years of age (inclusive).
    • Are not currently or have not participated in any other clinical studies within 30 days of Screening.
    • Ability to understand the requirements of the study, provide written informed consent, abide by the study procedures, and agree to return for the required assessments.
    • Subject is in good and stable health with no history or evidence of clinically relevant medical or neuropsychiatric illness.
    • Fluent in English, even if English is not the primary language. Subjects must hold a U.S. citizenship only for eligibility to participate.
  • Exclusion Criteria for Healthy Volunteer Subjects (HV)

    • Illicit drug use as determined by the saliva drug screen.
    • Current alcohol abuse as determined by the Investigator; or subject regularly consumed ≥3 alcoholic drinks/day during the 3 months prior to screening. One alcohol drink is approximately equivalent to: beer: 284 mL; wine: 125 mL (4 oz); or distilled spirits: 25 mL (1 oz).
    • Known (identifiable) biological family history of Schizophrenia spectrum disorders in a first or second degree relative.
    • Use of any first generation, sedating H1 antihistamines within 1 week prior to Screening or during the study. (see Medication Approval List)
    • Use of any sedative-hypnotic medications within 1 week prior to Screening or during the study. (see Medication Approval List)
    • Use of any other psychoactive medication known to interfere with ERP assessments within 1 week prior to Screening or during the study (see Medication Approval List).
    • Evidence or history of significant cognitive disorders, or other injuries, conditions, impairments, or situations that in the judgement of the Investigator would prevent safe and satisfactory completion of the study protocol.
    • Evidence or history of psychiatric illness as determined by the Mini International Neuropsychiatric Interview (MINI) for Psychotic Disorders.
    • Evidence of cognitive impairment as determined by performing ≥ 1.5 standard deviations lower compared to the age, sex, and education corrected mean on either the BACS Symbol Coding and/or Verbal Memory.
    • Significant intellectual disability as evidenced by a standardized WRAT-4 Reading Test standardized score < 70.
    • Unable to detect a 1000 and 2000 Hz tone at 40 dB in both ears.
    • Unable to tolerate the electrode cap for the duration of the testing session.
    • Known allergy to latex.
    • Use of products containing nicotine and/or caffeine 60 minutes prior to EEG/ERP testing.
  • Inclusion Criteria for Subjects with Schizophrenia (SZ)

    • Otherwise healthy male and female subjects 21-50 years of age (inclusive).
    • Are not currently or have not participated in any other clinical studies within 30 days of Screening.
    • Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments.
    • Current diagnosis of schizophrenia.
    • Duration of schizophrenia illness ≥ 1 years.
    • Clinically stable and in the residual (non-acute) phase of their illness for at least 6 weeks prior to the study as evidenced by a stable medication regimen and no recent hospitalizations for acute Schizophrenia. The subject's clinical stability is ultimately up to the Investigator.
    • Maintained on a stable regimen of antipsychotic and/or permitted concomitant medications for at least 6 weeks prior to screening and during the study.
    • Subjects receiving treatment with up to 2, first or second-generation antipsychotics or other concomitant medications commonly prescribed to this patient population, may be included. (see Allowed Medications List)
    • Fluent in English, even if English is not the primary language. Subjects must hold a U.S. citizenship only for eligibility to participate.
  • Exclusion Criteria for Subjects with Schizophrenia (SZ)

    • Illicit drug use as evidenced by the saliva drug screen.
    • Current alcohol abuse as determined by the Investigator; or subject regularly consumed ≥3 alcoholic drinks/day during the 3 months prior to screening. One alcohol drink is approximately equivalent to: beer: 284 mL; wine: 125 mL (4 oz); or distilled spirits: 25 mL (1 oz).
    • Use of any first-generation, sedating H1 antihistamines within 1 week prior to Screening or during the study (see Medication Approval List).
    • Use of any sedative-hypnotic medications within 1 week prior to Screening or during the study. (see Medication Approval List)
    • Use of any other psychoactive medication known to interfere with ERP assessments within 1 week prior to Screening or during the study (see Allowed Medications List).
    • Evidence or history of significant cognitive disorders, or other injuries, conditions, impairments, or situations that in the judgement of the Investigator would prevent safe and satisfactory completion of the study protocol.
    • Failure to confirm a diagnosis of Schizophrenia by the Investigator.
    • Significant intellectual disability as evidenced by a standardized WRAT-4 Reading Test score < 70.
    • Have no more than a moderate severity rating on hallucinations and delusions as evidenced by a PANSS items P1 ≥ 4 and P3 ≥ 4.
    • Have no more than a moderate severity rating on positive formal thought disorder as evidenced by a PANSS items G9 ≥ 4 and P2 ≥ 4.
    • Presence of more than minimal extrapyramidal symptoms as evidenced by a SAS score > 6.
    • Presence of more than minimal level of depressive symptoms as evidenced by a CDSS score ≥ 10.
    • Unable to detect a 1000 and 2000 Hz tone at 40 dB in both ears.
    • Unable to tolerate the electrode cap for the duration of the testing session.
    • Known allergy to latex.
    • Use of products containing nicotine and/or caffeine 60 minutes prior to EEG/ERP testing.
Sex/Gender
Sexes Eligible for Study: All
Ages 21 Years to 50 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04025502
Other Study ID Numbers EBS-A
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party ERP Biomarker Qualification Consortium
Study Sponsor ERP Biomarker Qualification Consortium
Collaborators
  • Novartis
  • Alkermes, Inc.
  • Anavex Life Sciences Corp.
  • Merck Sharp & Dohme Corp.
  • Takeda
  • Sage Therapeutics
  • H. Lundbeck A/S
  • Astellas Pharma Inc
  • Apex Innovative Sciences
  • Columbia University
  • COGNISION
Investigators
Principal Investigator: Marco Cecchi, PhD ERP Biomarker Qualification Consortium
PRS Account ERP Biomarker Qualification Consortium
Verification Date February 2021