Brain-derived Neurotrophic Factor and the Antidepressant Efficacy of Brain Stimulation
Primary Purpose
Treatment Resistant Depression
Status
Unknown status
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
Active rTMS-DLPFC
Active iTBS-DLPFC
Sham TBS-DLPFC or Sham rTMS-DLPFC
Sponsored by
About this trial
This is an interventional treatment trial for Treatment Resistant Depression
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.
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 HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Sham Comparator
Arm Label
Active rTMS-DLPFC
Active iTBS-DLPFC
Sham TBS-DLPFC or Sham rTMS-DLPFC
Arm Description
This active group will receive high-frequency repetitive TMS stimulation.
This active group will receive intermittent theta-burst TMS stimulation.
Patients in the sham group will receive the same iTBS or rTMS parameter stimulation, 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 4-week treatment at the end of TMS sessions and three month after.
improvement > 50 % of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)
Remission rate after 4-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.
The association between BDNF Polymorphism genotype and the antidepressant efficacy of brain stimulation
Val/Val, Met/Met, Val/Met genotype and the efficacy after receiving 4-week treatment. The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale
The association between the value of baseline brain metabolism and the antidepressant efficacy of brain stimulation
baseline PET/MRI.The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale.
The association between the value of Baseline treatment refractory level and the antidepressant efficacy of brain stimulation
Maudsley staging method. The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale.
The association between the value pf baseline Life event stress scale and the antidepressant efficacy of brain stimulation
Life event stress scale,range from 0 to 1467 with higher scores indicating more life event stress. The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale.
Changes in EEG band before and after brain stimulation
Perform rACC-engaging cognitive task(RECT) before 1-st treatment
Full Information
NCT ID
NCT04076124
First Posted
July 26, 2019
Last Updated
August 29, 2019
Sponsor
Taipei Veterans General Hospital, Taiwan
1. Study Identification
Unique Protocol Identification Number
NCT04076124
Brief Title
Brain-derived Neurotrophic Factor and the Antidepressant Efficacy of Brain Stimulation
Official Title
Different Forms of Prefrontal Transcranial Stimulation and Brain-derived Neurotrophic Factor in the Prediction of Antidepressant Efficacy of Brain Stimulation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 24, 2019 (Actual)
Primary Completion Date
September 30, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)
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 brain-derived neurotrophic factor(BDNF) polymorphisms and the antidepressant efficacy of transcranial magnetic stimulation device in patients with treatment-resistant depression. In a double-blind design, All patients are randomized to three groups, i.e.repetitive transcranial magnetic stimulation treatment, 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
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active rTMS-DLPFC
Arm Type
Experimental
Arm Description
This active group will receive high-frequency repetitive TMS stimulation.
Arm Title
Active iTBS-DLPFC
Arm Type
Experimental
Arm Description
This active group will receive intermittent theta-burst TMS stimulation.
Arm Title
Sham TBS-DLPFC or Sham rTMS-DLPFC
Arm Type
Sham Comparator
Arm Description
Patients in the sham group will receive the same iTBS or rTMS parameter stimulation, performing by a sham coil.
Intervention Type
Device
Intervention Name(s)
Active rTMS-DLPFC
Intervention Description
Participants in the rTMS active stimulation group will receive 4-week 10 Hz 120% of RMT to left DLPFC. Left side DLPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the L-DLPFC using a Magstim stimulator.
Intervention Type
Device
Intervention Name(s)
Active iTBS-DLPFC
Intervention Description
Participants in the intermittent TBS(iTBS) active stimulation group will receive 4-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to left DLPFC. Left side DLPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the L-DLPFC using a Magstim stimulator.
Intervention Type
Device
Intervention Name(s)
Sham TBS-DLPFC or Sham rTMS-DLPFC
Intervention Description
Half of the patients in the sham group received 4-week the same iTBS parameter stimulation (sham-iTBS), and the other half received the same rTMS parameter stimulation using a sham coil (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 4(day 20)
Secondary Outcome Measure Information:
Title
Response rate after 4-week treatment at the end of TMS sessions and three 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 4, week 16 (day 80)
Title
Remission rate after 4-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 4, week 16 (day 80)
Title
Changes in Clinical Global Index
Description
Clinical Global Index
Time Frame
Baseline, Week 1, Week 2, Week 3, Week 4(day 20)
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, Week 4(day 20)
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, Week 4(day 20)
Title
The association between BDNF Polymorphism genotype and the antidepressant efficacy of brain stimulation
Description
Val/Val, Met/Met, Val/Met genotype and the efficacy after receiving 4-week treatment. The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale
Time Frame
Baseline, Week 4(day 20)
Title
The association between the value of baseline brain metabolism and the antidepressant efficacy of brain stimulation
Description
baseline PET/MRI.The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale.
Time Frame
Baseline, Week 4(day 20)
Title
The association between the value of Baseline treatment refractory level and the antidepressant efficacy of brain stimulation
Description
Maudsley staging method. The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale.
Time Frame
Baseline, Week 4(day 20)
Title
The association between the value pf baseline Life event stress scale and the antidepressant efficacy of brain stimulation
Description
Life event stress scale,range from 0 to 1467 with higher scores indicating more life event stress. The antidepressant efficacy defined by the altered percentage of 17-item Hamilton Depression Rating Scale.
Time Frame
Baseline, Week 4(day 20)
Title
Changes in EEG band before and after brain stimulation
Description
Perform rACC-engaging cognitive task(RECT) before 1-st treatment
Time Frame
Day 1(pre-RECT, post RECT, post 1st treatment, pre-20th treatment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cheng-Ta Li, Professor
Phone
886 -2- 28757027
Ext
298
Email
ctli2@vghtpe.gov.tw
Facility Information:
Facility Name
Department of Psychiatry, Taipei Veterans General Hospital
City
Taipei City
ZIP/Postal Code
112
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng-Ta Li, Professor
Phone
+886-2-28757027
Ext
298
Email
ctli2@vghtpe.gov.tw; on5083@msn.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Brain-derived Neurotrophic Factor and the Antidepressant Efficacy of Brain Stimulation
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