Personalized Transcranial Magnetic Stimulation Treatment for Depression (APIC-TMS)

This proposal seeks to conduct a pragmatic single arm, open label pilot implementation to validate our individualized functional Magnetic Resonance Imaging (fMRI) connectome-guided localization approach for accelerated TMS among Asian patients with depression.

Participants will be patients with Major Depressive Disorder not responding to standard treatment, with no exclusions to fMRI or transcranial magnetic stimulation (TMS) (essentially metal implants in the head) and willing to participate in the pilot.

All participants will undergo MRI scans before and after the accelerated TMS treatment. The multi-session hierarchical Bayesian model (MS-HBM) approach will be used to estimate individualized connectome-guided target locations.

Patients will undergo accelerated TMS applied to individualized connectome-guided target locations (based on the MS-HBM approach).

Patients will undergo 10 sessions (each session lasting 10 min) spread out over 10 hours each day for 5 consecutive working days.

All clinical outcome data will be collected for each patient by a pre-defined questionnaire at four time points: at baseline, post-treatment, 1 month and 3 months during follow-up.

The clinical outcome data will be analyzed using linear regression or repeated analysis of variance (ANOVA) after adjusting for baseline clinical characteristics and socio-demographics. Trajectories of the clinical outcome data at baseline, post-treatment and all follow-up time points will be plotted and compared with time series statistical analysis models with the other clinical and socio-demographic characteristics included as confounders.

Study Overview

• Status: Recruiting
• Conditions: Depression
• Intervention / Treatment: Device: Individually Neuronavigated accelerated intermittent theta burst stimulation with Magpro X100

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Phern Chern Tor, MBBS; Phone Number: 63892000; Email: phern_chern_tor@imh.com.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • Institute of Mental Health
    • Contact: Phern-Chern Tor, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 21 years.
2. DSM-5 diagnosis of current Major Depressive Episode.
3. Montgomery-Asberg Depression Rating Scale score of 20 or more.
4. Inadequate response to an adequate trial (4 weeks) of at least one antidepressant medication.
5. Able to give informed consent.

Exclusion Criteria:

1. DSM-5 psychotic disorder
2. Drug or alcohol abuse or dependence (preceding 3 months).
3. Rapid clinical response required, e.g., high suicide risk.
4. Significant neurological disorder, which may pose increased risks with TMS, e.g., epilepsy.
5. Metal in the cranium, skull defects, pacemaker, cochlear implant, medication pump or other electronic device.
6. Pregnancy.
7. Unsuitable for MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Individually neuronavigated intermittent theta burst stimulation (Magpro X100) system for depression; Participants will receive an accelerated intermittent theta burst stimulation (iTBS) treatment delivered with a MagVenture MagPro X100 system (MagVenture A/S, Denmark) equipped with a butterfly shaped MagVenture Cool-B65 A/P coil. The treatment course is comprised of 10 treatment sessions daily for 5 consecutive workdays for a total of 50 sessions. Each iTBS session is approximately 10 minutes (depth corrected Resting Motor Threshold of 90%, 60 cycles of 10 bursts of three pulses at 50 Hz, repeated at 5 Hz; 2s on and 8s off; 1800 pulses per session; with a 50-minute interval between sessions). All iTBS sessions will be performed by staff trained and credentialed in TMS according to Singapore College of Psychiatrists guidelines.

Device: Individually Neuronavigated accelerated intermittent theta burst stimulation with Magpro X100; MagproX 100 and Axilium Cobot with Localite camera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Åsberg Depression Rating Scale (MADRS)	Clinician rated Depression rating scale, range of scores 0 to 60 with higher scores meaning a worse outcome	Baseline, immediately post treatment, 1 month and 3 months post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report) (QIDS-16)	Patient rated Depression rating scale, scored 0-27 with higher scores meaning a worse outcome	Baseline, (Days 1-5 of treatment), immediately after intervention, 1 month and 3 months post intervention
Montreal Cognitive Assessment (MoCA),	global cognitive functioning, scored 0 to 30 with higher scores meaning better outcome	Baseline, immediately post treatment, 1 month and 3 months post intervention
EuroQol- 5 Dimension (EQ-5D)	Quality of life scales, Visual analogue scale 0-100 with higher scores meaning better outcome	Baseline, immediately post treatment, 1 month and 3 months post intervention
Quality of Life Enjoyment and Satisfaction Questionnaire Short form (Q-LES-QS-SF)	Quality of life scales, scored 0-70 with higher scores meaning better outcome	Baseline, immediately post treatment, 1 month and 3 months post intervention

Other Outcome Measures

Outcome Measure	Time Frame
Correlation of changes in functional connectivity with changes in MADRS scores	Baseline, immediately post treatment

Collaborators and Investigators

• Sponsor: Institute of Mental Health, Singapore
• Collaborators: National University of Singapore

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 22, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: iTBS; Accelerated; neuronavigated
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: DSRB 2023/00397

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No