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

Treatment Resistant Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04037592
• Other study ID #: 2018-07-011C
• Status: Completed
• Phase: N/A
• Start date: July 24, 2019
• Est. completion date: January 31, 2021

Study information

• Verified date: August 2022
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: January 31, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

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.
• 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.
• 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

Locations

Country	Name	City	State
Taiwan	Department of Psychiatry, Taipei Veterans General Hospital	Taipei City

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Secondary	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)	Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Secondary	Remission rate after 3-week treatment	17-item Hamilton Depression Rating Scale =7 (range, 0 to 52, with higher scores indicating more depression)	Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Secondary	Changes in Clinical Global Index	Clinical Global Index	Baseline, Week 1, Week 2, Week 3
Secondary	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.	Baseline, Week 1, Week 2, Week 3
Secondary	Changes in Young Mania Rating Scale	Young Mania Rating Scale, range from 0 to 60 with higher scores indicating more severe manic symptoms.	Baseline, Week 1, Week 2, Week 3
Secondary	Baseline treatment refractory level and the further antidepressant efficacy of brain stimulation	Maudsley staging method	Baseline, Week 3
Secondary	Baseline brain connectivity and the further antidepressant efficacy of brain stimulation	baseline functional MRI	Baseline, Week 3
Secondary	the change of brain connectivity after 3-week iTBS treatment	the change in brain connectivity	Baseline, Week 3
Secondary	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.	Baseline, Week 3
Secondary	Changes in EEG band before and after brain stimulation	Perform rostral anterior cingulate cortex(rACC)-engaging cognitive task(RECT) before 1-st treatment	Day 1(pre-RECT, post RECT, post 1st treatment, pre-30th treatment)
Secondary	Baseline single-pulse stimulation and the further antidepressant efficacy of brain stimulation	baseline single-pulse stimulation	Baseline, Week 3
Secondary	Changes in single-pulse stimulation before and after brain stimulation	the change in single-pulse stimulation	Baseline, Week 3
Secondary	Baseline paired-pulse stimulation and the further antidepressant efficacy of brain stimulation	baseline paired-pulse stimulation	Baseline, Week 3
Secondary	Changes in paired-pulse stimulation before and after brain stimulation	the change in paired-pulse stimulation	Baseline, Week 3
Secondary	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.	Baseline, Week 1, Week 2, Week 3