Bipolar Proteomic Assay Validation Study

Study Overview
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Brief Summary
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The purpose of this study is to validate a set of signatures, based on a panel of proteomic markers, that discriminate BDI, BDII, and MDD in people seeking treatment for a depressive episode.

Detailed Description
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This is a hypothesis-driven confirmatory study to validate the diagnostic signature (model) for distinguishing BDI from MDD that also aims to optimize the models to discriminate BDII from MDD and BDI. A binary classification model, using linear discriminant analysis and based on 13 a priori-defined proteomic markers will aim to distinguish BDI from MDD. An alternative binary classification model based on multiple logistic regression and using 10 a priori -defined proteomic markers will aim for the same result. To improve the predictive performance of the signatures, items from self-report mood rating scales and treatment-emergent changes in proteomic markers will be analyzed. In addition, the study will examine if baseline or early treatment-emergent changes in proteomic markers predict treatment response.

Official Title
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A Validation Study to Measure the Impact of a Proteomic Assay in Distinguishing Bipolar I Disorder, Bipolar II Disorder, and Major Depressive Disorder in People Presenting With a Major Depressive Episode

Conditions
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Major Depressive Disorder, Bipolar I and Bipolar II

Intervention / Treatment
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* Other: Diagnostic test (LDT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with BDI, BDII, or MDD, confirmed with the Structured Clinical Interview for DSM-5 (SCID). Currently depressed for ≥4 weeks and ≤104 weeks, without psychotic features, MADRS score ≥ 20 (consistent with at least moderately-severe depression) YMRS score ≤ 8 (consistent with the absence of hypomanic symptoms) Exclusion Criteria: At high risk for suicide, defined as a score ≥4 on item 10 of the MADRS Current depression has psychotic features, diagnosed with the SCID Meeting criteria for severe alcohol, cannabis, or THC use disorders, as defined by DSM-5 and confirmed by the SCID, in the past 3 months, or meeting criteria for other substance use disorders of any severity (eg. cocaine use disorder). For substances other than alcohol, cannabis, and opioids, a positive drug screen at both the screening and baseline visits is also exclusionary. Caffeine and nicotine use disorders of any severity will not be exclusionary. Diagnosis of borderline personality disorder, diagnosed with the Zanarini Rating Scale for Borderline Personality Disorder. Medical conditions with neurological sequelae (eg. stroke, brain cancer, multiple sclerosis, loss of consciousness > 30 min, HIV) Severe chronic pain, at the discretion of the investigator Receiving treatment with high-potency immune-modulating medications, such as corticosteroids, chemotherapy, monoclonal antibodies, or disease-modifying agents for arthritis, multiple sclerosis Any acute unstable medical illness (at the discretion of the site investigator) In MDD patients: strong risk factors for bipolarity, including 1) short (1-3 day) mood elevations not meeting DSM-5 time criteria for hypomania; 2) a family history of BDI or BDII in a first-degree relative; and 3) a history of antidepressant-induced symptoms suggestive of bipolarity, particularly antidepressant-induced hypo/mania.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD<br>Patients diagnosed with Major Depressive Disorder | Other: Diagnostic test (LDT)<br>* Proteomic assay<br>|
| BPI<br>Patients diagnosed with bipolar I | Other: Diagnostic test (LDT)<br>* Proteomic assay<br>|
| BPII<br>Patients diagnosed with bipolar II | Other: Diagnostic test (LDT)<br>* Proteomic assay<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agreement between the model derived diagnosis (based on panel of serum proteomic markers) and the clinical diagnosis (confirmed by the SCID DSM-5) | Linear discriminant analysis and multiple logistic regression will be used to create three diagnostic models for the proteomic markers (BDI vs MDD, BDI vs BDII and BDII vs MDD). The patient's model diagnosis will be compared to the patient's clinical diagnoses (based on SCID DSM -5) and the proportion of concordant classifications will be calculated. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-report clinical rating scales (IDS-SR30, PHQ-9, MDQ, HCL-32 and TEMPS-A) | Additional clinical characterization of the patient and their depressive episode will be obtained through analysis of the self-report clinical rating scales and used to optimize the predictive performance of the proteomic signatures. | Baseline, Week 2 and Week 8 | 
| Changes in proteomic markers at Week 2 and Week 8 | Proteomic markers will be analyzed at weeks 2 and 8 to observe for any treatment-emergent changes to increase the predictive validity of the proteomic signatures. | Week 2 and Week 8 |