Bipolar Proteomic Assay Validation Study

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder, Bipolar I and Bipolar II
• Intervention / Treatment: Other: Diagnostic test (LDT)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 261

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Health Care, Department of Psychiatry
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota (UMN) Department of Psychiatry
  • Ohio
    • Mason, Ohio, United States, 45040
      • Lindner Center of HOPE/University of Cincinnati College of Medicine
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Western Psychiatric Institute and Clinic
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients seeking treatment for new on-set depression from academic programs and affiliated community mental health facilities (inpatient and outpatient

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MDD; Patients diagnosed with Major Depressive Disorder	Other: Diagnostic test (LDT); Proteomic assay
BPI; Patients diagnosed with bipolar I	Other: Diagnostic test (LDT); Proteomic assay
BPII; Patients diagnosed with bipolar II	Other: Diagnostic test (LDT); Proteomic assay

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response (> 50% improvement in MADRS score)	Distinguish responders from non-responders by measuring MADRS and determine if baseline or treatment-emergent changes in proteomic markers predict treatment response.	Baseline, Week 8
Remission (MADRS score < 8)	Distinguish remitters from non-remitters by measuring MADRS and determine if baseline or treatment-emergent changes in proteomic markers predict treatment response.	Baseline, Week 8
Antidepressant-induced hypo/mania (YMRS score > 12)	Compare incidence of antidepressant-induced hypo/manic episodes (defined as YMRS score > 12) to changes in proteomic markers to predict treatment response.	Baseline, Week 2, Week 4, Week 6

Collaborators and Investigators

• Sponsor: Myriad Genetic Laboratories, Inc.
• Collaborators: University of Minnesota

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): November 8, 2018
• Study Completion (ACTUAL): November 8, 2018

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (ESTIMATE): April 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Depressive Disorder, Major
• Other Study ID Numbers: EP-001