Mapping the Neural Circuits of Depression and Anxiety Using Personalized, Accelerated TMS and Deep Phenotyping (ADAPT)

August 13, 2026 updated by: National University Hospital, Singapore
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dysphoric target

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
Magpro X100, Axilium Cobot, Localite Camera
Experimental: Anxiosomatic target

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
Magpro X100, Axilium Cobot, Localite Camera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rank- Transformed Ratio of Beck Depression Inventory (BDI) to Beck Anxiety Inventory (BAI) change
Time Frame: Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inventory of Depression and Anxiety Symptoms-II (IDAS-II)
Time Frame: Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.
IDAS-II is an ordinal self-report scale measuring depression, anxiety, and bipolar symtpoms ranging from 99-495. Higher scores mean worse outcome.
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)
Time Frame: Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.
PSWQ is an ordinal self-report scale measuring pathological worry ranging from 16-80. Scores depend on whether the item is worded positively or negatively.
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
Time Frame: Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.
The investigators will test interactions between TMS Target and change in BDI and BAI (including baseline and weekly outcomes over one month) separately using repeated measures linear mixed effects models.
Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
TMS induced changes in resting-fMRI functional connectivity
Time Frame: Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.
The investigators will perform additional exploratory post-hoc analyses by analysing brain imaging changes before and after TMS treatment.
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
Time Frame: Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.
The investigators will also perform additional exploratory post-hoc analyses by analysing passive physiological data collected using an Oura ring throughout the study duration.
Baseline (before treatment), immediately after acute treatment (after 30 treatments over 1 week), and weekly during the 1-month follow-up period.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Collaborators

National University of Singapore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

July 31, 2029

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

July 2, 2026

First Submitted That Met QC Criteria

August 13, 2026

First Posted (Actual)

August 14, 2026

Study Record Updates

Last Update Posted (Actual)

August 14, 2026

Last Update Submitted That Met QC Criteria

August 13, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-1315

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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