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pBFS Guided High-dose rTMS Therapy for Treatment-Resistant Depression

Primary Purpose

Treatment-Resistant Depression

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Active rTMS with short inter-session interval
Sham rTMS with short inter-session interval
Active rTMS with long inter-session interval
Sponsored by
Changping Laboratory
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment-Resistant Depression

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Hospitalized/outpatient patients aged 18-65 years (inclusive), male or female. Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) for the depression disorder without psychotic symptoms, and currently experiencing the first episode or recurrence episode. Total HAMD17 score ≥18 before randomization. Total MADRS score ≥20 before randomization. A stable or no-drug use for at least 4 weeks before randomization. The type and dose of the antidepressant regimen remained unchanged throughout the study. No response (symptom improvement≥50%) in previous treatments with at least two antidepressants for a full dose and full course. Voluntarily participate in the trial and sign informed consent. Able to comply with the planned visit, examination and treatment plan, and other study procedures. Exclusion Criteria: Meet DSM-5 diagnostic criteria for other mental disorders (e.g., schizophrenia spectrum disorders, bipolar and related disorders, anxiety disorders, compulsion, and related disorders, trauma and stress-related disorders, etc.), or secondary depression; Patients with a cardiac pacemaker, cochlear implant, or other metal foreign body and any electronic equipment implanted in the body, patients with claustrophobia and other contraindications to magnetic resonance scanning, and patients with contraindications to rTMS treatment; Patients with serious or unstable diseases of the cardiovascular, liver, kidney, blood, endocrine, neurological system, and other systems or organs, especially those with organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain tumor, etc.) and a history of severe brain trauma as judged by the researcher; History of epilepsy (presence of at least 2 uninduced seizures more than 24 hours apart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months); Or currently received medications or other treatments that will lower the seizure threshold; History of ECT, rTMS, VNS, DBS, tDCS, light therapy, or other physical therapy related to mental illness within 3 months; Currently receiving or planning to start formal cognitive or behavioral therapy, or systemic psychological therapy (interpersonal therapy, dynamic therapy, cognitive behavioral therapy, etc.) during the trial. Substance abuse or dependence (including alcohol, drugs, and other psychoactive substances) in the past 1 year; Female of childbearing potential who plans to become pregnant during the trial. Female that is pregnant or breastfeeding. Patients in any clinical trials of other drugs or physical therapy within 1 month before the screening. Investigators think that was inappropriate to participate.

Sites / Locations

  • Beijing HuiLongGuan HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Sham Comparator

Active Comparator

Arm Label

Active rTMS with short inter-session interval

Sham rTMS with short inter-session interval

Active rTMS with long inter-session interval

Arm Description

Patients in this group will receive rTMS intervention with short inter-session intervals.

Patients in this group will receive sham rTMS intervention with short inter-session intervals.

Patients in this group will receive rTMS intervention with long inter-session intervals.

Outcomes

Primary Outcome Measures

Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to immediate post-treatment
The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher scores represent higher depression severity. The MADRS has an overall score ranging from 0 (no depression) to 60 (worst depression).

Secondary Outcome Measures

Change in MADRS, HAMD-17, and QIDS_SR from baseline to different time points post-treatment
The Hamilton Depression Rating Scale (HAMD) is the most widely used clinician-administered depression assessment scale. The HAMD-17 version consists of 17 items. Higher scores represent higher depression severity. The 16-item QIDS_SR is a widely used self-report instrument covering depressive symptoms incorporating nine Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnostic criteria for major depressive disorders. Higher scores represent higher depression severity.
Remission and response rates estimated using MADRS, HAMD, QIDS_SR
Three questionnaires were used to assess the response rate and remission rate of depression separately. Response is defined as an symptom improvement ≥50% on these scales; remission was defined as a score< 11 on MADRS, or <8 on HAMD, or <6 on QIDS_SR.
Safety measures using SSI and YMRS
Scale for Suicide Ideation (SSI) and Young Mania Rating Scale (YMRS) were used to estimated suicide ideation and manic symptoms

Full Information

First Posted
April 24, 2023
Last Updated
June 29, 2023
Sponsor
Changping Laboratory
Collaborators
Beijing HuiLongGuan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05842291
Brief Title
pBFS Guided High-dose rTMS Therapy for Treatment-Resistant Depression
Official Title
Personalized Brain Functional Sectors (pBFS) Guided High-dose rTMS Therapy for Treatment-resistant Depression: A Randomized, Double-Blind, Sham-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 19, 2023 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Changping Laboratory
Collaborators
Beijing HuiLongGuan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
We aim to evaluate the safety and efficacy of pBFS-guided high-dose rTMS therapy with short inter-session interval for patients with treatment-resistant depression
Detailed Description
Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. Currently, the FDA cleared the SAINT Neuromodulation System for the treatment of Treatment-Resistant Depression(TRD) over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been effective in a short period of time for treatment-resistant depression. The limitation of this approach includes the long inter-session interval (~50min) of the treatment, patients need to wait about 8 hours for 10 session's intervention per day. Therefore, it is urgent to explore the efficacy and safety of rTMS with a short inter-session interval (e.g. 20 min) that is more acceptable for TRD patients. After being informed about the study and potential risks. All patients giving written informed consent will undergo a screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a double-blind manner in a 1:1:1 ratio to the active short-interval rTMS group, active short-interval rTMS group, and active long-interval rTMS group. Then all participants will undergo a 5 day rTMS modulation followed by a four-week follow-up visit.

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 ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active rTMS with short inter-session interval
Arm Type
Experimental
Arm Description
Patients in this group will receive rTMS intervention with short inter-session intervals.
Arm Title
Sham rTMS with short inter-session interval
Arm Type
Sham Comparator
Arm Description
Patients in this group will receive sham rTMS intervention with short inter-session intervals.
Arm Title
Active rTMS with long inter-session interval
Arm Type
Active Comparator
Arm Description
Patients in this group will receive rTMS intervention with long inter-session intervals.
Intervention Type
Device
Intervention Name(s)
Active rTMS with short inter-session interval
Intervention Description
Participants in this group will receive ten sessions per day of 1800 pulses per session, at an inter-session interval of 20 min for 5 days. The individualized target will be generated using the personalized Brain Functional Sectors (pBFS) method.
Intervention Type
Device
Intervention Name(s)
Sham rTMS with short inter-session interval
Intervention Description
Participants in this group will receive ten sessions per day of 1800 pulses per session, at an inter-session interval of 20 min for 5 days, using sham stimulation coils that comprehensively mimic the active condition. The individualized target will be generated using the personalized Brain Functional Sectors (pBFS) method.
Intervention Type
Device
Intervention Name(s)
Active rTMS with long inter-session interval
Intervention Description
Participants in this group will receive ten sessions per day of 1800 pulses per session, at an inter-session interval of 50 min for 5 days. The individualized target will be generated using the personalized Brain Functional Sectors (pBFS) method.
Primary Outcome Measure Information:
Title
Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to immediate post-treatment
Description
The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher scores represent higher depression severity. The MADRS has an overall score ranging from 0 (no depression) to 60 (worst depression).
Time Frame
Baseline, Day 5 (Immediate Post-treatment)
Secondary Outcome Measure Information:
Title
Change in MADRS, HAMD-17, and QIDS_SR from baseline to different time points post-treatment
Description
The Hamilton Depression Rating Scale (HAMD) is the most widely used clinician-administered depression assessment scale. The HAMD-17 version consists of 17 items. Higher scores represent higher depression severity. The 16-item QIDS_SR is a widely used self-report instrument covering depressive symptoms incorporating nine Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnostic criteria for major depressive disorders. Higher scores represent higher depression severity.
Time Frame
Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
Title
Remission and response rates estimated using MADRS, HAMD, QIDS_SR
Description
Three questionnaires were used to assess the response rate and remission rate of depression separately. Response is defined as an symptom improvement ≥50% on these scales; remission was defined as a score< 11 on MADRS, or <8 on HAMD, or <6 on QIDS_SR.
Time Frame
Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
Title
Safety measures using SSI and YMRS
Description
Scale for Suicide Ideation (SSI) and Young Mania Rating Scale (YMRS) were used to estimated suicide ideation and manic symptoms
Time Frame
Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Hospitalized/outpatient patients aged 18-65 years (inclusive), male or female. Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) for the depression disorder without psychotic symptoms, and currently experiencing the first episode or recurrence episode. Total HAMD17 score ≥18 before randomization. Total MADRS score ≥20 before randomization. A stable or no-drug use for at least 4 weeks before randomization. The type and dose of the antidepressant regimen remained unchanged throughout the study. No response (symptom improvement≥50%) in previous treatments with at least two antidepressants for a full dose and full course. Voluntarily participate in the trial and sign informed consent. Able to comply with the planned visit, examination and treatment plan, and other study procedures. Exclusion Criteria: Meet DSM-5 diagnostic criteria for other mental disorders (e.g., schizophrenia spectrum disorders, bipolar and related disorders, anxiety disorders, compulsion, and related disorders, trauma and stress-related disorders, etc.), or secondary depression; Patients with a cardiac pacemaker, cochlear implant, or other metal foreign body and any electronic equipment implanted in the body, patients with claustrophobia and other contraindications to magnetic resonance scanning, and patients with contraindications to rTMS treatment; Patients with serious or unstable diseases of the cardiovascular, liver, kidney, blood, endocrine, neurological system, and other systems or organs, especially those with organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain tumor, etc.) and a history of severe brain trauma as judged by the researcher; History of epilepsy (presence of at least 2 uninduced seizures more than 24 hours apart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months); Or currently received medications or other treatments that will lower the seizure threshold; History of ECT, rTMS, VNS, DBS, tDCS, light therapy, or other physical therapy related to mental illness within 3 months; Currently receiving or planning to start formal cognitive or behavioral therapy, or systemic psychological therapy (interpersonal therapy, dynamic therapy, cognitive behavioral therapy, etc.) during the trial. Substance abuse or dependence (including alcohol, drugs, and other psychoactive substances) in the past 1 year; Female of childbearing potential who plans to become pregnant during the trial. Female that is pregnant or breastfeeding. Patients in any clinical trials of other drugs or physical therapy within 1 month before the screening. Investigators think that was inappropriate to participate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Meiling Li, Ph.D.
Phone
010-80726688
Email
meilingli@cpl.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hesheng Liu, Ph.D.
Organizational Affiliation
Changping Laboratory
Official's Role
Study Chair
Facility Information:
Facility Name
Beijing HuiLongGuan Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100096
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Song Chen, MD

12. IPD Sharing Statement

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pBFS Guided High-dose rTMS Therapy for Treatment-Resistant Depression

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