Biosignatures of Latuda for Bipolar Depression

Study Overview
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Brief Summary
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The study proposes to conduct a pilot study of biological predictors of lurasidone response in bipolar depression.

Detailed Description
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The study proposes to enroll 20 participants with a bipolar disorder who are currently in an episode of major depression.Magnetic resonance imaging (MRI), recordings of brain electrical activity (EEG), and psychological testing to explore possible predictors of lurasidone treatment response will be conducted. Blood samples will be collected for a future study of blood protein predictors of response. After testing, participants will receive an open-label 8-week trial of lurasidone (Latuda™) at approved dosage levels. Participants who attain remission of their major depressive episode will be eligible for a six-month continuation phase to explore predictors of sustained response to continuation treatment. Data analyses will use statistical testing to explore potential biological predictors of lurasidone response. This will provide a framework for clarifying which patients are best suited to this treatment and begin to develop a model for precision treatment of this difficult-to-treat disorder.

Official Title
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Identification of Biosignatures for Lurasidone (Latuda) Response in Bipolar Depression

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: Lurasidone (Latuda)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18- 60 Outpatients with a primary Diagnostic and Statistical Manual of the American Psychiatric Association, Fourth Edition (DSM-IV) diagnosis of Bipolar Disorder I, II, or NOS (Not Otherwise Specified) Current episode of Major Depression At least moderate severity of depression Agrees to, and is eligible for, electroencephalogram (EEG) / psychological testing, magnetic resonance imaging (MRI), and blood draws Provides informed consent Exclusion Criteria: Current drug or alcohol abuse/dependence, except nicotine (within 6 months for dependence; 2 for abuse) Taking any of the following exclusionary medications: antipsychotics, anticonvulsants, mood stabilizers, stimulants, antidepressant medications, medications with significant interactions with lurasidone, except during the washout prior to testing and blood collection Unstable medical condition, including significant liver disease, hypothyroidism (i.e., condition not adequately stabilized for 3 months), and conditions likely to require hospitalization or with a life expectancy of < 6 mos.* Patients considered at significant risk for suicide Inadequate understanding of English Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods; plan to become pregnant within 12 months Contraindications to MRI (e.g. ferromagnetic body implants, history of metal working, etc.) Have epilepsy, neuromuscular disorder, or tardive dyskinesia Require immediate hospitalization for psychiatric disorder Require medications for a general medical condition that contraindicate any study medication** Receiving or have received during the index episode vagus nerve stimulation, electroconvulsive therapy, transcranial magnetic stimulation, or other somatic treatments Allergy to, or other medical contraindication to lurasidone treatment Currently enrolled in another research study, and participation in that study contraindicates participation Clinically significant screening laboratory abnormalities (* see below) Currently taking an effective mood stabilizer and/or antidepressant regimen Inability to undergo a three week medication-free period, including history of significant clinical deterioration from past periods off medication or when medication dosage was reduced, including mania, severe depression, etc. Any reason not listed herein that would make participation in the study hazardous *Medical criteria for exclusion: Untreated hypertension: > 140/90 Torr on repeated measurement (If hypertension becomes stabilized, subject may enroll in study) Hepatitis: any liver function test > 2x the upper limit of normal Renal failure: estimated Glomerular Filtration Rate (eGFR, corrected for body surface area) repeatedly < 30 mL/min Hypothyroidism: thryrotropin stimulating hormone level > upper limit of normal (unless accompanied by other euthyroid indices and the confirmation by an internist or endocrinologist that this does not represent hypothyroidism) Anemia: hemoglobin < 10 grams/deciliter (borderline hemoglobin must be of known origin, stable, and not clinically significant)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Lurasidone (Latuda)<br>All study participants will receive open-label Latuda. | Drug: Lurasidone (Latuda)<br>* Antipsychotic medication approved for use with Bipolar disorder<br>* Other names: Latuda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Rating Scale for Depression (MADRS) | The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Nine of the items are based upon patient report, and one is on the rater's observation during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). | Baseline | 
| Montgomery-Asberg Rating Scale for Depression (MADRS) at Week8 | The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Nine of the items are based upon patient report, and one is on the rater's observation during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar Disorder, depression, Bipolar depression