NCT07766291

Brief Summary

This proposal seeks to carry out a double-blinded, randomized, comparative study that investigates neurobehavioral changes induced by personalized, anxiosomatic and dysphoric network guided accelerated intermittent-theta burst (iTBS) using dense functional Magnetic Resonance Imaging (fMRI) sampling in participants with treatment-resistant depression (TRD) and moderate/high levels of anxiety.

Trial Health

63
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P25-P50 for not_applicable

Timeline
41mo left

Started Sep 2026

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 2, 2026

Completed
1 month until next milestone

First Posted

Study publicly available on registry

August 14, 2026

Completed
18 days until next milestone

Study Start

First participant enrolled

September 1, 2026

Expected
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2029

5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2029

Last Updated

August 14, 2026

Status Verified

August 1, 2026

Enrollment Period

2.9 years

First QC Date

July 2, 2026

Last Update Submit

August 13, 2026

Conditions

Depression Disorder

Keywords

DepressionNeuronavigatediTBSRCTAcceleratedAnxiety

Outcome Measures

Primary Outcomes (1)

  • Rank- Transformed Ratio of Beck Depression Inventory (BDI) to Beck Anxiety Inventory (BAI) change

    The primary outcome will be the rank-transformed ratio of BDI change to BAI change (e.g. A patient has a 50% reduction in BDI and a 25% reduction in BAI, giving a BDI:BAI ratio of 50% ÷ 25% = 2.0. Another patient has a 40% reduction in BDI and a 25% reduction in BAI, giving a BDI:BAI ratio of 40% ÷ 25% = 1.6. Higher ratios indicate a relatively greater improvement in depression compared with anxiety within each patient. This ratio is then ranked across all patients.).

    Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

Secondary Outcomes (3)

  • Inventory of Depression and Anxiety Symptoms-II (IDAS-II)

    Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

  • Penn State Worry Questionnaire (PSWQ)

    Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

  • Interaction between TMS target and change in BDI and BAI

    Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

Other Outcomes (2)

  • TMS induced changes in resting-fMRI functional connectivity

    Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

  • Passive physiological metrics

    Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

Study Arms (2)

Dysphoric target

EXPERIMENTAL

Participants will receive individualized connectome-guided accelerated iTBS at their dysphoric target. Participants will receive an accelerated iTBS treatment delivered with a MagVenture MagPro X100 system (MagVenture A/S, Denmark) equipped with a butterflu shaped MagVenture Cool-B65 A/P coil. The treatment course is comprised of 6 treatment sessions daily for 5 consecutive workdays for a total of 30 sessions. Each iTBS session is approximately 10 minutes (depth corrected Resting Motor Threshold of 90%, 60 cycles of 10 bursts of three pulses at 50Hz, repeated at 5Hz; 2s on and 8s off; 1800 puolses 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: Individualized connectome-guided accelerated iTBS

Anxiosomatic target

EXPERIMENTAL

Participants will receive individualized connectome-guided accelerated iTBS at their anxiosomatic target. Participants will receive an accelerated iTBS treatment delivered with a MagVenture MagPro X100 system (MagVenture A/S, Denmark) equipped with a butterflu shaped MagVenture Cool-B65 A/P coil. The treatment course is comprised of 6 treatment sessions daily for 5 consecutive workdays for a total of 30 sessions. Each iTBS session is approximately 10 minutes (depth corrected Resting Motor Threshold of 90%, 60 cycles of 10 bursts of three pulses at 50Hz, repeated at 5Hz; 2s on and 8s off; 1800 puolses 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: Individualized connectome-guided accelerated iTBS

Interventions

Individualized connectome-guided accelerated iTBSDEVICE

Magpro X100, Axilium Cobot, Localite Camera

Anxiosomatic targetDysphoric target

Eligibility Criteria

Age21 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male/female aged 21-70
  • Diagnosis of MDD as validated by MINI
  • Non-response to adequate trial (4 weeks) of at least two MDD medication as verified by the study clinician
  • BDI score of 20 or above; BAI score of 16 or above
  • Able to give informed consent
  • Able to understand English

You may not qualify if:

  • DSM-5 psychotic disorder
  • Drug or alcohol abuse or dependence (preceding 3 months)
  • Rapid clinical response required, e.g., high suicide risk
  • Significant neurological disorder, which may pose increased risks with TMS, e.g., epilepsy
  • Metal in the cranium, skull defects, pacemaker, cochlear implant, medication pump or other electronic device
  • Pregnancy
  • Unsuitable for MRI
  • With recent TMS or ECT treatment in past 3 months
  • Multiple stimulant medications

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National University Hospital, Singapore

Singapore, Singapore

Location

MeSH Terms

Conditions

DepressionAnxiety Disorders

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehaviorMental Disorders

Central Study Contacts

Phern Chern Tor, MBBS

CONTACT

+65 6908 2222cip@nuhs.edu.sg

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 2, 2026

First Posted

August 14, 2026

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

July 31, 2029

Study Completion (Estimated)

December 31, 2029

Last Updated

August 14, 2026

Record last verified: 2026-08

Data Sharing

IPD Sharing
Will not share

Locations

SG(1)