Response Predictors of Theta-burst Stimulation for Depression

Study Overview
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Brief Summary
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The study consists of an open label trial designed to treat adult depression with TBS. Our aim is to build capacity in neuroimaging analyses by performing magnetic resonance imaging (MRI) assessments at baseline and after 7-10 days of treatment onset in 70 patients. The scientific goal is to test a hypothesis about treatment action: that TBS will reduce negative bias (which causally maintains negative mood) after 1 week of treatment, and patients who show this neurocognitive change will be the ones who go on to respond clinically after 6 weeks.

Detailed Description
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Depressive disorders are among the leading causes of incapacity and disability worldwide. The burden of depression is expected to increase and is associated with negative impact on clinical conditions and physical and cognitive abilities. Given the limited efficacy of antidepressant drugs, novel treatments such as theta-burst brain stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), are being developed. However, to further advance the field towards treatment personalisation, increasing understanding of TBS antidepressant mechanisms and identifying treatment responders are important issues. Moreover, no studies have used neuroimaging in TBS trials in depression yet. Our group in Brazil is a leading brain stimulation centre, although neuroimaging expertise is lacking. We will conduct an open label trial designed to treat adult depression with TBS. Our aim is to build capacity in neuroimaging analyses by performing magnetic resonance imaging (MRI) assessments at baseline and after 7-10 days of treatment onset in 70 patients. The scientific goal is to test a hypothesis about treatment action: that TBS will reduce negative bias (which causally maintains negative mood) after 1 week of treatment, and patients who show this neurocognitive change will be the ones who go on to respond clinically after 6 weeks. Scientifically, this proposal and its outcomes will help advance towards next-generation precision brain stimulation, by incorporating cognitive/neuroimaging readouts that inform about mechanism and individual response.

Official Title
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Use of Functional Neuroimaging Biomarkers as Early Predictors of Response to Theta-burst Stimulation Treatment in Depression

Conditions
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Depression

Intervention / Treatment
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* Other: Theta burst stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: participants aged from 18 to 65 years, with HDRS score ≥ 14, with MDD confirmed by MINI structured interview. - Exclusion Criteria: other mental disorders (alcohol or other substance dependence, bipolar disorder, psychotic disorders or dementia), severe clinical or neurological disorders, suicidal ideation, presence of psychotic symptoms, severe depression characterized by HDRS score > 28, manic symptoms characterized by score > 8 in the Young Mania Rating Scale. In addition, patients with specific contraindications to magnetic stimulation or magnetic resonance imaging will be excluded, such as having any metallic implants, epilepsy or any electronic component in the head.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Active TBS.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Theta-burst stimulation (TBS)<br>Receive active iTBS, 1800 pulses, 100% MT over dlPFC. | Other: Theta burst stimulation<br>* It consists of 20 sessions of iTBS over the dlPFC.<br>* Other names: TBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Rating Scale scores (17-item version) | Clinician-administered depression assessment scale. Score range = 0 - 52 (higher scores mean worse outcome). | Week 0 (baseline) and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale scores (MADRS) | Clinician-administered depression assessment scale. Score range = 0 - 60 (higher scores mean worse outcome). | Week 0 (baseline) and Week 6 | 
| Change in Young Mania Rating Scale (YMRS) scores | Clinician-administered scale that measures hypomania/mania symptoms. Score range = 0 - 60 (higher scores mean worse outcome). | Week 0 (baseline) and Week 6 | 
| Facial Expression Recognition Test (FERT) | Cognitive test used to detect emotional bias. | Week 0 (baseline) and Week 2. | 
| Change in Positive and Negative Affect Schedule scores (PANAS) | Self-report questionnaire to measure both positive and negative affect. Positive Affect Score: scores can range from 10 - 50, with higher scores representing higher levels of positive affect (better outcome). Negative Affect Score: scores can range from 10 - 50, with higher scores representing higher levels of negative affect (worse outcome). | Week 0 (baseline) and Week 6 | 
| Change in State-Trait Anxiety Inventory scores (STAI-T and STAI-S) | Self-report measures of state and trait anxiety. The range of possible scores for each subscale (STAI-T and STAI-S) varies from a minimum score of 20 to a maximum score of 80, with higher scores meaning worse outcome. | Week 0 (baseline) and Week 6 | 
| Change in functional and structural neuroimaging exam | Neuroimaging exam used to measure both functional and structural aspects of the brain as possible predictors of clinical response to treatment. | baseline and after two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, fMRI, response predictors, TBS