Maintenance Individualized Neuromodulation and Depression-detection Via Sensors for Early Treatment (MINDSET)

MINDSET: Maintenance Individualized Neuromodulation and Depression-detection Via Sensors for Early Treatment

This proposal seeks to carry out a prospective, single-arm open label study aimed at sustaining treatment-resistant depression (TRD) response in patients with TRD who had responded to prior individualized resting-state functional connectivity (rs-FC)-guided intermittent theta burst stimulation (iTBS). It also seeks to detect and predict relapse risk by integrating rs-FC iTBS with a TMS-adapted needs-based symptom-titrated algorithm based longitudinal ECT (STABLE) maintenance scheduling algorithm, and passive digital biomarkers.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression Disorder
• Intervention / Treatment: Device: Individualized resting-state functional connectivity-guided iTBS; Diagnostic test: Symptom-titrated algorithm-based longitudinal ECT (STABLE) algorithm

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Phern Chern Tor, MBBS; Phone Number: +65 6908 2222; Email: cip@nuhs.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • National University Hospital, Singapore
    • Contact: Phern Chern Tor, MBBS; Phone Number: +65 6908 2222; Email: cip@nuhs.edu.sg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male/ female aged ≥ 21 to ≤ 70 years old
• Able to give informed consent
• Able to understand English
• DSM-V diagnosis of current/ past major depressive disorder (MDD) episode
• Non-response to an adequate trial (4 weeks) of at least 1 MDD medication as verified by a study clinician
• Ability to comply with passive wearable use and weekly mobile assessments
• Have previously completed a course of individualized, functional connectivity-guided accelerated iTBS and shown a clinical response (as defined by a ≥50% improvement in MADRS score against baseline, any time within 3 months following an acute iTBS course)
• Able to comply with the full 12-month protocol inclusive of continuous digital monitoring

Exclusion Criteria:

• DSM-5 psychotic disorder
• Drug or alcohol abuse or dependence (preceding 3 months)
• Significant neurological disorder, which may pose increased risks with TMS, e.g., epilepsy
• Metal in the cranium, skull defects, pacemaker, cochlear implant, medication infusion pump or any other electronic implants or devices
• Tattoos containing ferromagnetic ink or permanent piercings
• Pregnancy
• Currently on multiple CNS stimulant medications (2 or more at maximal clinical doses)
• Participant does not have the capacity to provide consent

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: Individualized, resting-state functional connectivity-guided accelerated iTBS

Device: Individualized resting-state functional connectivity-guided iTBS; MagPro X100, Axilium Cobot, Localite Camera; Diagnostic test: Symptom-titrated algorithm-based longitudinal ECT (STABLE) algorithm; The STABLE relapse detection algorithm provides a symptom-driven retreatment scheduling. It is validated to prolong TRD response to electroconvulsive therapy (ECT) while minimizing overtreatment. The algorithm will be adapted for TMS and will be used to determine the need for maintenance iTBS treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time spent in response	The investigators will compute the percentage of time spent in treatment-resistant depression (TRD) response over the course of each participant's time in the study. TRD response is defined by fulfilling the low relapse criteria in accordance with the (symptom-titrated algorithm-based longitudinal ECT) STABLE algorithm. In this study, low relapse potential would be a Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≤9 or a MADRS score of 10-19 with <3-point increase from baseline, and <5-point increase in 4 consecutive weeks at any point in the study. MADRS is an ordinal clinician-rated scale measuring depression ranging from 0-60. Higher scores mean a worse outcome.	Baseline, and weekly for 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptomatology (16-item) Self-Report (QIDS-SR16)	QIDS-SR16 is an ordinal self-report scale measuring depressive symptomatology ranging from 0-27. Higher scores mean a worse outcome.	Baseline, and weekly for 12 months.
Beck Anxiety Index (BAI)	BAI is an ordinal self-report scale measuring cognitive and physical anxiety symptoms ranging from 0-63. Higher scores mean a worse outcome.	Baseline, and weekly for 12 months.
General Anxiety Disorder-7 (GAD-7)	GAD-7 is an ordinal self-report scale measuring general anxiety ranging from 0-21. Higher scores mean a worse outcome.	Baseline, and weekly for 12 months.
EuroQol 5-Dimension (EQ-5D)	EQ-5D is an ordinal self-report scale measuring the health-related quality of life graded across severity levels. It includes a Visual Analogue Scale (VAS), which ranges from 0-100, with a higher score meaning a better outcome.	Full questionnaire is administered at baseline, and weekly for 12 months. The VAS section of the questionnaire is logged daily for 12 months.
Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)	Q-LES-Q-SF is an ordinal self-report scale measuring satisfaction with daily life and functioning, ranging from 0-70. Higher scores mean a better outcome.	Baseline, and weekly for 12 months.
Sheehan Disability Scale (SDS)	SDS is an ordinal self-report scale measuring how symptoms affect functional impairment across work/ school, social life, and family/ home responsibilities, ranging from 0-10 for each domain. Higher scores mean a worse outcome.	Baseline, and weekly for 12 months.
Montgomery-Åsberg Depression Rating Scale (MADRS)	MADRS is an ordinal clinician-rated scale measuring depression ranging from 0-60. Higher scores mean a worse outcome.	Baseline, and weekly for 12 months.

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Collaborators: National University of Singapore

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 18, 2026
• First Submitted That Met QC Criteria: August 18, 2026
• First Posted (Actual): August 21, 2026

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Maintenance; Relapse; Treatment resistant depression; iTBS; Neuronavigated
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Behavioral Symptoms; Mood Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Behavior; Recurrence; Depression; Depressive Disorder, Treatment-Resistant; Mathematical Concepts; Algorithms
• Other Study ID Numbers: 2026-0652

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