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

NCT04025502 | Completed DMC

• 1 other identifier: EBS-A
• Study Type: observational
• Target: 161
• Locations: 1 country
• Sites: 4

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.

Conditions

Schizophrenia

Keywords

ERP; EEG; Event-related potential; MMN; Schizophrenia; Electroencephalogram; Mismatch Negativity; N100; P3a; P3b

Outcome Measures

Primary Outcomes (13)

• Amplitude (in microvolts) for parameters from the ERP tests.

  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

  12-18 months

• Latency (in milliseconds) for parameters from the ERP tests.

  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

  12-18 months

• Task accuracy from the behavioral response during the active, auditory oddball ERP test.

  Task accuracy as a percentage of correct behavioral responses during the active, auditory oddball ERP test will be collected as a primary endpoint.

  12-18 months

• Reaction time from the behavioral response during the active, auditory oddball ERP test.

  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.

  12-18 months

• Total Power from the auditory steady-state response (ASSR) paradigm.

  Total Power (measured in µv2/Hz) will be collected during the ASSR paradigm as a primary endpoint.

  12-18 months

• Inter-trial coherence (ITC) from the auditory steady-state response (ASSR) paradigm.

  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.

  12-18 months

• Absolute Power for Pharmaco-EEG parameters per IPEG guidelines.

  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

  12-18 months

• Relative Power for Pharmaco-EEG parameters per IPEG guidelines.

  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

  12-18 months

• Dominant frequency in the Alpha frequency band per IPEG guidelines

  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.

  12-18 months

• Theta/Beta ratio and Slow Wave index per IPEG guidelines.

  Theta/Beta ratio and Slow Wave index (Alpha/Delta+Theta) measured in percentage will be collected from the Resting State EEG as primary endpoints.

  12-18 months

• Functional assessments as derived from the Brief Assessment of Cognition in Schizophrenia (BACS).

  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

  12-18 months

• Functional assessments as derived from the Positive and Negative Symptom Scale for Schizophrenia (PANSS).

  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

  12-18 months

• Functional assessments as derived from the Virtual Reality Functional Capacity Assessment Tool (VRFCAT).

  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

  12-18 months

Secondary Outcomes (1)

• Correlations between EEG/ERP measures and psychometric measures in Schizophrenia subjects.

  12-18 months

Study Arms (2)

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.

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.

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

Interventions

Event-Related Potentials (ERP) and Electroencephalogram (EEG) testing with the COGNISION® System DEVICE

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.

Healthy Volunteer Subjects (HV); Subjects with Schizophrenia (SZ)

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Otherwise healthy male and female subjects 21-50 years of age (inclusive).

Sponsors & Collaborators

• ERP Biomarker Qualification Consortium: lead
• Novartis: collaborator
• Alkermes, Inc.: collaborator
• Anavex Life Sciences Corp.: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Takeda: collaborator
• Sage Therapeutics: collaborator
• H. Lundbeck A/S: collaborator
• Astellas Pharma Inc: collaborator
• Apex Innovative Sciences: collaborator
• Columbia University: collaborator
• COGNISION: collaborator

Study Sites (4)

Collaborative Neuroscience Network, LLC

Garden Grove, California, 92845, United States

Location

Collaborative Neuroscience Network, LLC

Torrance, California, 90502, United States

Location

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (6)

• Jobert M, Wilson FJ, Ruigt GS, Brunovsky M, Prichep LS, Drinkenburg WH; IPEG Pharmaco-EEG Guidelines Committee. Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG). Neuropsychobiology. 2012;66(4):201-20. doi: 10.1159/000343478. Epub 2012 Oct 12.

  PMID: 23075830 BACKGROUND

• Umbricht D, Krljes S. Mismatch negativity in schizophrenia: a meta-analysis. Schizophr Res. 2005 Jul 1;76(1):1-23. doi: 10.1016/j.schres.2004.12.002. Epub 2005 Jan 23.

  PMID: 15927795 BACKGROUND

• Light GA, Hsu JL, Hsieh MH, Meyer-Gomes K, Sprock J, Swerdlow NR, Braff DL. Gamma band oscillations reveal neural network cortical coherence dysfunction in schizophrenia patients. Biol Psychiatry. 2006 Dec 1;60(11):1231-40. doi: 10.1016/j.biopsych.2006.03.055. Epub 2006 Aug 7.

  PMID: 16893524 BACKGROUND

• Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.

  PMID: 9881538 BACKGROUND

• Buchanan RW, Davis M, Goff D, Green MF, Keefe RS, Leon AC, Nuechterlein KH, Laughren T, Levin R, Stover E, Fenton W, Marder SR. A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull. 2005 Jan;31(1):5-19. doi: 10.1093/schbul/sbi020. Epub 2005 Feb 16.

  PMID: 15888422 BACKGROUND

• Buchanan RW, Keefe RS, Umbricht D, Green MF, Laughren T, Marder SR. The FDA-NIMH-MATRICS guidelines for clinical trial design of cognitive-enhancing drugs: what do we know 5 years later? Schizophr Bull. 2011 Nov;37(6):1209-17. doi: 10.1093/schbul/sbq038. Epub 2010 Apr 21.

  PMID: 20410237 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Saliva drug screen to rule out illicit drug use for all three visits (Screening visit, Baseline visit, and Retest visit).

MeSH Terms

Conditions

Schizophrenia

Interventions

Electroencephalography

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Marco Cecchi, PhD

  ERP Biomarker Qualification Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2019
• First Posted: July 19, 2019
• Study Start: October 7, 2019
• Primary Completion: December 29, 2020
• Study Completion: January 31, 2021
• Last Updated: February 24, 2021

Record last verified: 2021-02

Locations

US (4)