UMIN-CTR Clinical Trial

Public title

Comparisons of Prefrontal Inhibition and Excitation Between Prefrontal Intermittent Theta-Burst Stimulation and 10-Hz Repetitive Transcranial Magnetic Stimulation for Treating Refractory Depression: A Sham-Control Neuroimaging Study

Acronym

Antidepressant efficacy of piTBS, rTMS, and sham

Scientific Title

Comparisons of Prefrontal Inhibition and Excitation Between Prefrontal Intermittent Theta-Burst Stimulation and 10-Hz Repetitive Transcranial Magnetic Stimulation for Treating Refractory Depression: A Sham-Control Neuroimaging Study

Scientific Title:Acronym

Antidepressant efficacy of piTBS, rTMS, and sham

Region

Asia(except Japan)

Condition

The evidence so far suggests that inhibitory function, such as GABAa-receptor-related and GABAb-receptor-related inhibitory function in the DLPFC, is key to treatment responses in MDD. Prolonged intermittent theta-burst stimulation(piTBS) could be effective through the modulation of prefrontal excitatory and inhibitory function. In addition, previous literature provided the evidence that 2-weeks left-sided DLPFC-piTBS had similar antidepressant efficacy with the 4-6weeks standard left-sided DLPFC-10HzrTMS. However, the following questions remain to be answered: (1)4-weeks left-sided DLPFC-piTBS could provide better antidepressant efficacy than 4-weeks left-sided DLPFC-10HzrTMS; (2)the potentially different effects of 4-weeks piTBS and rTMS on PFC inhibitory functions, and (3) the identification of reliable biomarkers, including EEG signals, that could reliably predict the antidepressant effects of 4-weeks rTMS/piTBS intervention.

Classification by specialty

Psychiatry

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The purpose of this study is to evaluate the antidepressant efficacy of 4-weeks prolonged intermittent theta-burst stimulation (piTBS) and clarify the neruoplasticity effects of different TMS parameters, such as iTBS and rTMS,by evaluating their prefrontal excitatory/inhibitory function and brain glucose metabolism in patients with treatment-resistant depression, and to identify biomarkers that can predict antidepressant effects. This will assist clinicians in selecting stimulation treatment parameters and improving response rates.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Improvement in depression severity, measured by a percentage change in 17-items Hamilton Depression Rating Scale(HDRS-17) score (% HDRS-17) before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham).

Key secondary outcomes

1. The response rate (defined as a >= 50% reduction compared with the baseline HDRS-17 score) and the remission rate (defined as an HDRS-17 score <= 7).
2. Safety
3. the changes of TMS-EEG parameters before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham)
4. the changes of regional brain glucose metabolism before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham)
5. the changes of prefrontal EEG before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham)
6. the changes of cognitive function, measured by Test of Attentional Performance and Go-Nogo test, before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham)
7. the changes of functional connectivities before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham)
8. the correlation between antidepressant efficacy and baseline prefrontal function, measured by EEG, TMS-EEG indices and glucose metabolism and functional connectivities and EEG.
9. the correlation between antidepressant efficacy and baseline mood-related brain area, measured by glucose metabolism and functional connectivities.
10. the correlation between antidepressant efficacy and the changes of glucose metabolism and functional connectivities on the mood-related brain area.
11. the correlation between antidepressant efficacy and the changes of TMS-EEG and EEG indices on prefrontal cortex.
12. the correlation between antidepressant efficacy and patients' characteristic (e.g., treatment refractoriness)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Cluster

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

Concealment

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Interventions/Control_1

Group A (piTBS group): A three-pulse 50Hz wave delivered every 200ms at 80% active motor threshold, with stimulation for 2 seconds followed by an 8-second rest, for 60 cycles, totaling 1800 pulses/session, for a total of 20 sessions(4 weeks)

Interventions/Control_2

Group B (10Hz rTMS group): 10Hz at 120% resting motor threshold, with stimulation for 4 seconds followed by a 16-second rest, for 75 cycles, totaling 3000 pulses/session, for a total of 20 sessions(4 weeks)

Interventions/Control_3

Sham group: half of the patients following the parameters of Group A and the other half following the parameters of Group B, but stimulated by standard sham coil (Magstim(R)), for a total of 20 sessions(4 weeks)

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

21

years-old

<=

Age-upper limit

70

years-old

>=

Gender

Male and Female

Key inclusion criteria

The diagnosis of recurrent MDD is based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria (American Psychiatric Association, 1994).

Patients qualified to participate in the study if they failed to respond to at least 1 adequate antidepressant treatment for their current episode (e.g., failed to achieve 50% improvement in depression to an equivalent daily dose of 10-20 mg of escitalopram for at least 8 weeks).

MDD patients would be recruited only if the score of the 17-item Hamilton Depression Rating Scale (HDRS-17) is 18 or more and the score of a Clinical Global Impression Severity is 4 or more.

All participants were on stable antidepressant regimens or no antidepressant therapy for at least 4 weeks prior to this trial.

Key exclusion criteria

(1)A lifetime psychiatric diagnosis of psychotic disorder, bipolar disorder, organic mental disorder, substance use disorder (based on DSM-IV criteria), and a lifetime medical history of major systemic illness and neurological disorder records(e.g., seizure, cerebrovascular disease, stroke, meningitis and traumatic brain injury)
(2)A history of brain surgery, brain implants (e.g., neurostimulators, clip), and cardiac pacemakers and any mental device or implant in the body (e.g. neurostimulators, electrodes, cochlear implant)
(3)Any major brain organic insults (e.g., brain arteriovenous malformation, cerebral aneurysm, primary or secondary tumors in central nervous system)
(4)Having active suicidal intent, or high suicidality if score of the third item of HDRS-17 is 4 in recent one week.
(5)Women in pregnancy.
(6)Claustrophobia: people cannot stay in a closed environment (e.g., MRI scan)
(7)Presence of any other condition that has the potential to prevent study completion or may confound the outcome assessments (e.g. refusal to sign the informed consent, no meet the inclusion criteria after recruitment)

Target sample size

60

Name of lead principal investigator

1st name	Cheng-Ta
Middle name
Last name	Li

Organization

Taipei Veterans General Hospital, Taipei, Taiwan

Division name

Department of Psychiatry

Zip code

112

Address

No.201, Sec. 2, Shih-Pai Road, Beitou district, Taipei, Taiwan

TEL

+886-2-28757027

Email

on5083@msn.com

Name of contact person

1st name	Cheng-Ta
Middle name
Last name	Li

Organization

Taipei Veterans General Hospital, Taipei, Taiwan

Division name

Department of Psychiatry

Zip code

112

Address

No.201, Sec. 2, Shih-Pai Road, Beitou district, Taipei, Taiwan

TEL

+886-2-28757027

Homepage URL

Email

on5083@msn.com

Institute

Taipei Veterans General Hospital, Taipei, Taiwan

Institute

Department

Personal name

Organization

Taipei Veterans General Hospital, Taipei, Taiwan

Organization

Division

Category of Funding Organization

Outside Japan

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Institutional Review Board, Taipei Veterans General Hospital, Taipei, Taiwan

Address

NO.201, SEC. 2, SHIPAI RD, Taipei City, Taiwan

Tel

886-2-2875-7384

Email

irbopinion@vghtpe.gov.tw

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2024

Year

10

Month

28

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Enrolling by invitation

Date of protocol fixation

2024

Year

08

Month

01

Day

Date of IRB

2024

Year

09

Month

13

Day

Anticipated trial start date

2024

Year

10

Month

28

Day

Last follow-up date

2026

Year

10

Month

28

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2024

Year

10

Month

27

Day

Last modified on

2024

Year

10

Month

27

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000063946