Clinical trial NCT02746367: Bipolar Proteomic Assay Validation Study
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Major Depressive Disorder, Bipolar I and Bipolar II
Lead sponsor: Myriad Genetic Laboratories, Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Minnesota
First posted: 2016-04-21
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Agreement between the model derived diagnosis (based on panel of serum proteomic markers) and the clinical diagnosis (confirmed by the SCID DSM-5)
timeFrame: Baseline
Secondary outcomes:
measure: Self-report clinical rating scales (IDS-SR30, PHQ-9, MDQ, HCL-32 and TEMPS-A)
timeFrame: Baseline, Week 2 and Week 8
measure: Changes in proteomic markers at Week 2 and Week 8
timeFrame: Week 2 and Week 8
Other outcomes:
measure: Treatment response (> 50% improvement in MADRS score)
timeFrame: Baseline, Week 8
measure: Remission (MADRS score < 8)
timeFrame: Baseline, Week 8
measure: Antidepressant-induced hypo/mania (YMRS score > 12)
timeFrame: Baseline, Week 2, Week 4, Week 6
Locations:
city: Iowa City
country: United States
facility: University of Iowa Health Care, Department of Psychiatry
state: Iowa
city: Minneapolis
country: United States
facility: University of Minnesota (UMN) Department of Psychiatry
state: Minnesota
city: Mason
country: United States
facility: Lindner Center of HOPE/University of Cincinnati College of Medicine
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Western Psychiatric Institute and Clinic
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
References: