Dorsomedial Prefrontal Cortex and the Antidepressant Efficacy of Theta Burst Stimulation in Depressed Patients

Overview

This study evaluates an association between different dosage and the antidepressant efficacy of theta burst stimulation in patients with treatment-resistant depression. In a double-blind design, All patients are randomized to three groups, i.e. standardized dosage intermittent theta-burst stimulation treatment, high dosage intermittent theta-burst stimulation treatment or sham treatment.

Full Title of Study: “Dorsomedial Prefrontal Cortex and the Antidepressant Efficacy of Theta Burst Stimulation in Depressed Patients and Its Predictors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Outcomes Assessor)
  • Study Primary Completion Date: December 31, 2020

Interventions

  • Device: Active standardized iTBS-DMPFC
    • Participants in the standardized dosage(600 pulse) of intermittent TBS(iTBS) active stimulation group will receive 3-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to bilateral DMPF, twice a day. Bilateral side DMPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the DMPFC using a Magstim stimulator.
  • Device: Active high-dosage iTBS-DMPFC
    • Participants in the standardized dosage(1800pulse) of intermittent TBS(iTBS) active stimulation group will receive 3-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to bilateral DMPF, twice a day. Bilateral side DMPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the DMPFC using a Magstim stimulator.
  • Device: Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC
    • Half of the patients in the sham group received 3-week the same standardized iTBS parameter stimulation (standardized sham-iTBS), and the other half received the same high dosage iTBS parameter stimulation using a sham coil (high dosage sham-rTMS), which also improved the blinding process

Arms, Groups and Cohorts

  • Experimental: Active standardized iTBS-DMPFC
    • This active group will receive standardized dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)
  • Experimental: Active high-dosage iTBS-DMPFC
    • This active group will receive high dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)
  • Sham Comparator: Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC
    • Patients in the sham group will receive the same standardized or high-dosage iTBS performing by a sham coil

Clinical Trial Outcome Measures

Primary Measures

  • Percentage change in 17-item Hamilton Depression Rating Scale
    • Time Frame: Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
    • the altered percentage of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)

Secondary Measures

  • Response rate after 3-week treatment at the end of iTBS sessions and three and six month after.
    • Time Frame: Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
    • improvement > 50 % of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)
  • Remission rate after 3-week treatment
    • Time Frame: Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
    • 17-item Hamilton Depression Rating Scale ≤7 (range, 0 to 52, with higher scores indicating more depression)
  • Changes in Clinical Global Index
    • Time Frame: Baseline, Week 1, Week 2, Week 3
    • Clinical Global Index
  • Changes in depression severity, rated by self-reported
    • Time Frame: Baseline, Week 1, Week 2, Week 3
    • Depression and Somatic Symptoms Scale, range from 0 to 66 with higher scores indicating more depressive and somatic symptom.
  • Changes in Young Mania Rating Scale
    • Time Frame: Baseline, Week 1, Week 2, Week 3
    • Young Mania Rating Scale, range from 0 to 60 with higher scores indicating more severe manic symptoms.
  • Baseline treatment refractory level and the further antidepressant efficacy of brain stimulation
    • Time Frame: Baseline, Week 3
    • Maudsley staging method
  • Baseline brain connectivity and the further antidepressant efficacy of brain stimulation
    • Time Frame: Baseline, Week 3
    • baseline functional MRI
  • the change of brain connectivity after 3-week iTBS treatment
    • Time Frame: Baseline, Week 3
    • the change in brain connectivity
  • Baseline Life event stress scale and the further antidepressant efficacy of brain stimulation
    • Time Frame: Baseline, Week 3
    • Life event stress scale,range from 0 to 1467 with higher scores indicating more life event stress.
  • Changes in EEG band before and after brain stimulation
    • Time Frame: Day 1(pre-RECT, post RECT, post 1st treatment, pre-30th treatment)
    • Perform rostral anterior cingulate cortex(rACC)-engaging cognitive task(RECT) before 1-st treatment

Participating in This Clinical Trial

Inclusion Criteria

  • Male or female, 21 to 70 years of age.
  • Diagnosed with the recurrent Major depressive disorder (MDD) and currently having a Major Depressive Episode (MDE)
  • Participants failed to respond to at least one adequate antidepressant treatment in their current episode
  • Participants have a Clinical Global Impression – Severity score of at least 4 and a total score of at least 18 on the Hamilton Depression Rating Scale (HDRS-17) at both screening and baseline visits ( Day -14 and Day 0)
  • Participants must discontinue their antidepressant medications at least for one week ( at least two weeks if Fluoxetine) prior to the TMS intervention and keep antidepressant-free during the study duration.

Exclusion Criteria

  • a lifetime psychiatric history of bipolar disorder, schizophrenia, psychotic disorders, or organic mental disorder including substance abuse and dependence (based on DSM-IV criteria)
  • Participants with a lifetime medical history of major systemic illness and clinically significantly abnormal screening examination that might affect safety, study participation, or confound interpretation of study results.
  • Participants with a lifetime medical history of neurological disorder records (e.g., stroke, seizure, traumatic brain injury, post brain surgery), brain implants (neurostimulators), cardiac pacemakers
  • Women with breastfeeding or pregnancy
  • Participants with a current strong suicidal risk (i.e., a score of 4 on item 3 of the HDRS-17)

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Taipei Veterans General Hospital, Taiwan
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Cheng-Ta Li, Professor, 886 -2- 28757027, ctli2@vghtpe.gov.tw

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