Biomarker-guided rTMS for Treatment Resistant Depression
Last updated on July 2021Recruitment
- Recruitment Status
- Not yet recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Major Depressive Disorder
- Treatment Resistant Depression
- Type
- Interventional
- Phase
- Phase 3
- Design
- Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: Human subjects in the proposed protocol will be randomized to receive a) biotype-guided 10Hz rTMS to the left DLPFC or to the DMPFC; b) rTMS targeted to the opposite site; and c) standard-of-care 10Hz left DLPFC rTMS. Participants will receive screening and diagnostic interviews, phenotypic assessment (including demographic information, cognitive assessments, and behavioral functioning), structured clinical interviews, and magnetic resonance imaging (including structural and functional MRI).Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 65 years
- Gender
- Both males and females
Description
Major depressive disorder (MDD) is a leading cause of global disability, and approximately 30% of MDD patients are resistant to antidepressant pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an FDA-cleared intervention with p...
Major depressive disorder (MDD) is a leading cause of global disability, and approximately 30% of MDD patients are resistant to antidepressant pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an FDA-cleared intervention with proven efficacy in treatment-resistant depression, but only 30-40% of these patients achieve remission after a single course. Other studies have shown that rTMS targeting the dorsomedial prefrontal cortex (DMPFC) is comparably effective, but biomarkers for informing target site selection do not exist. Diagnostic heterogeneity has been an obstacle to biomarker discovery efforts. Recently, we developed and validated an approach to diagnose four novel MDD subtypes or "biotypes' defined by resting state functional connectivity (RSFC) patterns and predicting differing antidepressant responses at the individual level to rTMS. This pivotal trial will test a novel, biotype-guided treatment selection strategy motivated by the hypothesis that an individual patient's likelihood of responding to left DLFPC vs.DMPFC rTMS is determined in part by individual differences in 1) the degree to which their symptoms are driven by dysfunction in specific cerebral network targets comprising Valence Systems; and 2) the degree to which dysfunction in those targets can be modulated by stimulating the left DLPFC or DMPFC. Subjects (N=405; 203 from this site) will be randomized to receive a) biotype-guided 10 Hz rTMS targeting the DMPFC or left DLPFC; b) to a disconfirmation arm receiving rTMS targeting the opposite site; and c) to a third arm receiving FDA-cleared, standard-of-care 10 hertz (HZ) rTMS targeting the left DLFPC, regardless of biotype. All patients will be assessed before and after treatment on a battery of fMRI, behavioral, and clinical assessments. The primary goal is to confirm the efficacy of a novel RSFC biomarker-guided approach to differential treatment selection in treatment resistant depression.
Tracking Information
- NCT #
- NCT04041479
- Collaborators
- National Institute of Mental Health (NIMH)
- Investigators
- Principal Investigator: Conor Liston, MD, PhD Weill Medical College of Cornell University
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