Biosignatures of Latuda for Bipolar Depression

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

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

Study Overview

• Status: Completed
• Conditions: Bipolar Depression
• Intervention / Treatment: Drug: Lurasidone (Latuda)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18- 60
2. 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)
3. Current episode of Major Depression
4. At least moderate severity of depression
5. Agrees to, and is eligible for, electroencephalogram (EEG) / psychological testing, magnetic resonance imaging (MRI), and blood draws
6. Provides informed consent

Exclusion Criteria:

1. Current drug or alcohol abuse/dependence, except nicotine (within 6 months for dependence; 2 for abuse)
2. 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
3. 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.*
4. Patients considered at significant risk for suicide
5. Inadequate understanding of English
6. Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods; plan to become pregnant within 12 months
7. Contraindications to MRI (e.g. ferromagnetic body implants, history of metal working, etc.)
8. Have epilepsy, neuromuscular disorder, or tardive dyskinesia
9. Require immediate hospitalization for psychiatric disorder
10. Require medications for a general medical condition that contraindicate any study medication**
11. Receiving or have received during the index episode vagus nerve stimulation, electroconvulsive therapy, transcranial magnetic stimulation, or other somatic treatments
12. Allergy to, or other medical contraindication to lurasidone treatment
13. Currently enrolled in another research study, and participation in that study contraindicates participation
14. Clinically significant screening laboratory abnormalities (* see below)
15. Currently taking an effective mood stabilizer and/or antidepressant regimen
16. 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.

17. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: Sunovion
• Investigators: Principal Investigator: Patrick J McGrath, MD, New York State Psychiatric Institute

Publications and helpful links

General Publications

• Lan MJ, Pantazatos SP, Ogden RT, Rubin-Falcone H, Hellerstein D, McGrath PJ, Mann JJ. Resting State MRI Amplitude of Low Frequency Fluctuations Associated With Suicidal Ideation in Bipolar Depression. J Clin Psychiatry. 2022 Mar 30;83(3):21m14054. doi: 10.4088/JCP.21m14054.

Helpful Links

• Depression Evaluation Service (site location) website
• Institutional department website

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 11, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: depression; Bipolar Disorder; Bipolar depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Lurasidone Hydrochloride
• Other Study ID Numbers: #6954; 6954 (Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)