ERG Components in Schizophrenia and Bipolar Disorder Type I

Study Overview
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Brief Summary
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This study will further assess ERG components obtained with different ERG devices, to be considered in a prediction model for each diagnosis. The prediction models are diaMentis proprietary software used as an ERG-based diagnostic test (classified as a Software as Medical Device, SaMD) to support the diagnosis of schizophrenia and bipolar disorder type I. They involve the processing and analysis of specific retinal biosignatures (RSPA) with the support of statistical and mathematical modelling processes e.g. machine learning and statistical learning.

Detailed Description
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The technology under development by diaMentis is defined as a Software as a Medical Device (SaMD); it will be used in combination with an electroretinogram (ERG). This study will be performed using three different ERG devices, currently marketed and cleared by the health authorities (Espion, UTAS and RETeval) to support the analytical, scientific and performance validity of the SaMD. Anomalies detected by ERG provide an objective measure that may reflect specific underlying dysfunctions in patients and thus hold promise to confirm relevant biosignatures in psychiatric disorders. Significant differences between patients with SZ, BPI and control subjects have been found despite confounding factors; this trial is required to better define the impact of patient characteristics on ERG features with a potential to refine the interpretation of results. This is a multicenter study. Three hundred subjects will be enrolled into three groups: 100 SZ patients, 100 BPI patients and 100 control subjects (healthy volunteers). The primary objective is to further characterize the ERG components in SZ and BPI patients in order to develop prediction models that discriminate each pathology. The secondary objectives are the evaluation of the repeatability and reproducibility of the analysis of the ERG components in control subjects, the assessment of the reliability of ERG prediction score for patients following a repeat test, and the evaluation of the impact of different ERG devices on the data generated and the prediction models.

Official Title
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Assessment of ERG Components to Discriminate Between Schizophrenia and Bipolar Disorder Type I

Conditions
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Schizophrenia, Bipolar I Disorder

Intervention / Treatment
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* Device: ERG assessment (RSPA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give written informed consent; 18 to 50 years old; Patient with a likely diagnosis of SZ or BPI for at least 12 months, that resulted in a diagnosis of SZ or BPI with a Structured Clinical Interview for DSM-5 (SCID-5-CT); Control subjects who do not have a lifetime diagnosis of SZ, BP, other psychotic disorder, recurrent mood disorder or have not met criteria for a major depression episode in the last 12 months according to DSM-V criteria. Exclusion Criteria: Control subjects taking antipsychotic drugs (other prescription medicines are allowed); Control subjects with a first-degree relative with SZ, BP, other psychotic disorder or recurrent major depressive disorder; Patient currently in an acute inpatient unit and not stable (i.e. experiencing an acute exacerbation of psychosis or mania); Diagnosed dementia, Parkinson's disease, autism or other pervasive developmental disorders or seizure disorders (such as epilepsy); Substance use disorder within the last 6 months; Any known diagnosis of ophthalmological abnormalities, such as diabetic retinopathy, glaucoma, change in intraocular pressure, macular degeneration, other retinal pathologies, congenital color vision deficiencies, strabismus or cataract; Any person contra-indicated for an ERG test, including active corneal or conjunctival disease (e.g. pink eye or conjunctivitis), infection or a ruptured globe; Subjects in recovery phase following cataract surgery or post LASIK refractive surgery or trabeculectomy or any surgical/laser intervention, suspected penetrating ocular injury, ocular prosthesis or severe photophobia; Any person unable to or unwilling to participate in a psychiatric evaluation or ERG testing, including, in the clinical judgment of the Principal investigator, subjects with cognitive impairment that compromises their ability to participate meaningfully in a SCID-5-CT interview. Any subject during the course of the study that is pregnant or intends on becoming pregnant and/or receives or intends to receive fertility treatments. Subjects becoming pregnant during study will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control subjects<br>Control subjects who do not have a lifetime diagnosis of SZ, BP, other psychotic disorder, recurrent mood disorder or have not met criteria for a major depression episode in the last 12 months according to DSM-V criteria. | Device: ERG assessment (RSPA)<br>* Processing and analysis of retinal signals<br>|
| Patients with schizophrenia (SZ)<br>Patient with a diagnosis of schizophrenia for at least 12 months, that resulted in a diagnosis with a Structured Clinical Interview for DSM-5 (SCID-5-CT). | Device: ERG assessment (RSPA)<br>* Processing and analysis of retinal signals<br>|
| Patients with bipolar disorder Type I (BP1)<br>Patient with a diagnosis of bipolar disorder Type 1 for at least 12 months, that resulted in a diagnosis with a Structured Clinical Interview for DSM-5 (SCID-5-CT). | Device: ERG assessment (RSPA)<br>* Processing and analysis of retinal signals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in ERG components vs control ERG with full-field ERG stimulation conditions. | ERG components are retinal signal features (signal amplitude vs time) in the electrical signal recorded up to 100 msec post stimulation. | Three ERG assessments within 6 weeks. | 
| Differences in ERG components vs control ERG with Photopic Negative Response (PhNR) ERG stimulation conditions. | ERG components are retinal signal features (signal amplitude vs time) in the electrical signal recorded up to 250 msec post stimulation. | Three ERG assessments within 6 weeks. | 
| Differences in ERG components vs control ERG with On-Off ERG stimulation conditions. | ERG components are retinal signal features (signal amplitude vs time) in the electrical signal recorded up to 300 msec post stimulation. | Three ERG assessments within 6 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinal Signal, Schizophrenia, Bipolar I Disorder, Support to diagnostic, ERG, Mental Disorder