Response Predictors of Theta-burst Stimulation for Depression (TBS)

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

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.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Other: Theta burst stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 05403-903
      • Instituto de Psiquiatria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: participants aged from 18 to 65 years, with HDRS score ≥ 14, with MDD confirmed by MINI structured interview.

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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.

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: Theta-burst stimulation (TBS); Receive active iTBS, 1800 pulses, 100% MT over dlPFC.	Other: Theta burst stimulation; It consists of 20 sessions of iTBS over the dlPFC.; Other Names: TBS

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Academy of Medical Sciences, UK
• Investigators: Principal Investigator: Andre R Brunoni, MD, PhD, FACULDADE DE MEDICINA DA USP

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2021
• Primary Completion (Actual): November 28, 2022
• Study Completion (Actual): November 28, 2023

Study Registration Dates

• First Submitted: July 16, 2021
• First Submitted That Met QC Criteria: July 16, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: depression; fMRI; TBS; response predictors
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 43768721.4.0000.0068; NAFR12\1010 (Other Grant/Funding Number: Academy of Medical Sciences UK)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No