Brain-derived Neurotrophic Factor and the Antidepressant Efficacy of Brain Stimulation

Treatment Resistant Depression Clinical Trial

Official title:

Different Forms of Prefrontal Transcranial Stimulation and Brain-derived Neurotrophic Factor in the Prediction of Antidepressant Efficacy of Brain Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04076124
• Other study ID #: V107C-123
• Status: Recruiting
• Phase: N/A
• Start date: July 24, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: August 2019
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: Cheng-Ta Li, Professor
• Phone: 886 -2- 28757027
• Email: ctli2[@]vghtpe.gov.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• 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.

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 rTMS-DLPFC
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.
• Active iTBS-DLPFC
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.
• Sham TBS-DLPFC or Sham rTMS-DLPFC
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.

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 4(day 20)
Secondary	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)	Baseline, Week 1, Week 2, Week 3, Week 4, week 16 (day 80)
Secondary	Remission rate after 4-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 4, week 16 (day 80)
Secondary	Changes in Clinical Global Index	Clinical Global Index	Baseline, Week 1, Week 2, Week 3, Week 4(day 20)
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, Week 4(day 20)
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, Week 4(day 20)
Secondary	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	Baseline, Week 4(day 20)
Secondary	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.	Baseline, Week 4(day 20)
Secondary	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.	Baseline, Week 4(day 20)
Secondary	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.	Baseline, Week 4(day 20)
Secondary	Changes in EEG band before and after brain stimulation	Perform rACC-engaging cognitive task(RECT) before 1-st treatment	Day 1(pre-RECT, post RECT, post 1st treatment, pre-20th treatment)