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

A Multi-Center Study of Event-Related Potential (ERP) Biomarkers in Subjects With Schizophrenia and Healthy Volunteer Subjects

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.

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.

• 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.