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

Primary Purpose

Treatment Resistant Depression

Status
Completed
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
Active standardized iTBS-DMPFC
Active high-dosage iTBS-DMPFC
Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC
Sponsored by
Taipei Veterans General Hospital, Taiwan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.
  • Participants also failed to respond to one complete left-sided DLPFC 10Hz rTMS/piTBS treatment course.

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)

Sites / Locations

  • Department of Psychiatry, Taipei Veterans General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Sham Comparator

Arm Label

Active standardized iTBS-DMPFC

Active high-dosage iTBS-DMPFC

Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC

Arm Description

This active group will receive standardized dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)

This active group will receive high dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)

Patients in the sham group will receive the same standardized or high-dosage iTBS performing by a sham coil

Outcomes

Primary Outcome Measures

Percentage change in 17-item Hamilton Depression Rating Scale
the altered percentage of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)

Secondary Outcome Measures

Response rate after 3-week treatment at the end of iTBS sessions and three and six month after.
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
17-item Hamilton Depression Rating Scale ≤7 (range, 0 to 52, with higher scores indicating more depression)
Changes in Clinical Global Index
Clinical Global Index
Changes in depression severity, rated by self-reported
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
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
Maudsley staging method
Baseline brain connectivity and the further antidepressant efficacy of brain stimulation
baseline functional MRI
the change of brain connectivity after 3-week iTBS treatment
the change in brain connectivity
Baseline Life event stress scale and the further antidepressant efficacy of brain stimulation
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
Perform rostral anterior cingulate cortex(rACC)-engaging cognitive task(RECT) before 1-st treatment
Baseline single-pulse stimulation and the further antidepressant efficacy of brain stimulation
baseline single-pulse stimulation
Changes in single-pulse stimulation before and after brain stimulation
the change in single-pulse stimulation
Baseline paired-pulse stimulation and the further antidepressant efficacy of brain stimulation
baseline paired-pulse stimulation
Changes in paired-pulse stimulation before and after brain stimulation
the change in paired-pulse stimulation
Change in anxiosomatic cluster symptoms derived 17-item Hamilton Depression Rating Scale
the altered anxiosomatic cluster symptoms (range, 0 to 26, with higher scores indicating more severe anxiosomatic symptoms).The anxiosomatic cluster symptoms comprised nine items derived from HDRS-17: early insomnia, middle insomnia, slowness or retardation, psychic anxiety, autonomic anxiety, gastrointestinal symptoms, somatic symptoms, genital symptoms, and hypochondriasis.

Full Information

First Posted
July 26, 2019
Last Updated
August 28, 2022
Sponsor
Taipei Veterans General Hospital, Taiwan
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1. Study Identification

Unique Protocol Identification Number
NCT04037592
Brief Title
Dorsomedial Prefrontal Cortex and the Antidepressant Efficacy of Theta Burst Stimulation in Depressed Patients
Official Title
Dorsomedial Prefrontal Cortex and the Antidepressant Efficacy of Theta Burst Stimulation in Depressed Patients and Its Predictors
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
July 24, 2019 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
January 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taipei Veterans General Hospital, Taiwan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active standardized iTBS-DMPFC
Arm Type
Experimental
Arm Description
This active group will receive standardized dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)
Arm Title
Active high-dosage iTBS-DMPFC
Arm Type
Experimental
Arm Description
This active group will receive high dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)
Arm Title
Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC
Arm Type
Sham Comparator
Arm Description
Patients in the sham group will receive the same standardized or high-dosage iTBS performing by a sham coil
Intervention Type
Device
Intervention Name(s)
Active standardized iTBS-DMPFC
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Active high-dosage iTBS-DMPFC
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC
Intervention Description
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
Primary Outcome Measure Information:
Title
Percentage change in 17-item Hamilton Depression Rating Scale
Description
the altered percentage of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)
Time Frame
Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Secondary Outcome Measure Information:
Title
Response rate after 3-week treatment at the end of iTBS sessions and three and six month after.
Description
improvement > 50 % of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)
Time Frame
Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Title
Remission rate after 3-week treatment
Description
17-item Hamilton Depression Rating Scale ≤7 (range, 0 to 52, with higher scores indicating more depression)
Time Frame
Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Title
Changes in Clinical Global Index
Description
Clinical Global Index
Time Frame
Baseline, Week 1, Week 2, Week 3
Title
Changes in depression severity, rated by self-reported
Description
Depression and Somatic Symptoms Scale, range from 0 to 66 with higher scores indicating more depressive and somatic symptom.
Time Frame
Baseline, Week 1, Week 2, Week 3
Title
Changes in Young Mania Rating Scale
Description
Young Mania Rating Scale, range from 0 to 60 with higher scores indicating more severe manic symptoms.
Time Frame
Baseline, Week 1, Week 2, Week 3
Title
Baseline treatment refractory level and the further antidepressant efficacy of brain stimulation
Description
Maudsley staging method
Time Frame
Baseline, Week 3
Title
Baseline brain connectivity and the further antidepressant efficacy of brain stimulation
Description
baseline functional MRI
Time Frame
Baseline, Week 3
Title
the change of brain connectivity after 3-week iTBS treatment
Description
the change in brain connectivity
Time Frame
Baseline, Week 3
Title
Baseline Life event stress scale and the further antidepressant efficacy of brain stimulation
Description
Life event stress scale,range from 0 to 1467 with higher scores indicating more life event stress.
Time Frame
Baseline, Week 3
Title
Changes in EEG band before and after brain stimulation
Description
Perform rostral anterior cingulate cortex(rACC)-engaging cognitive task(RECT) before 1-st treatment
Time Frame
Day 1(pre-RECT, post RECT, post 1st treatment, pre-30th treatment)
Title
Baseline single-pulse stimulation and the further antidepressant efficacy of brain stimulation
Description
baseline single-pulse stimulation
Time Frame
Baseline, Week 3
Title
Changes in single-pulse stimulation before and after brain stimulation
Description
the change in single-pulse stimulation
Time Frame
Baseline, Week 3
Title
Baseline paired-pulse stimulation and the further antidepressant efficacy of brain stimulation
Description
baseline paired-pulse stimulation
Time Frame
Baseline, Week 3
Title
Changes in paired-pulse stimulation before and after brain stimulation
Description
the change in paired-pulse stimulation
Time Frame
Baseline, Week 3
Title
Change in anxiosomatic cluster symptoms derived 17-item Hamilton Depression Rating Scale
Description
the altered anxiosomatic cluster symptoms (range, 0 to 26, with higher scores indicating more severe anxiosomatic symptoms).The anxiosomatic cluster symptoms comprised nine items derived from HDRS-17: early insomnia, middle insomnia, slowness or retardation, psychic anxiety, autonomic anxiety, gastrointestinal symptoms, somatic symptoms, genital symptoms, and hypochondriasis.
Time Frame
Baseline, Week 1, Week 2, Week 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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. Participants also failed to respond to one complete left-sided DLPFC 10Hz rTMS/piTBS treatment course. 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)
Facility Information:
Facility Name
Department of Psychiatry, Taipei Veterans General Hospital
City
Taipei City
ZIP/Postal Code
112
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
No

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

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