Mapsd Dual-target cTBS (Auditory Cortex and M1) for Generalized Anxiety Disorder (Dual-ACM1-GAD)

February 4, 2026 updated by: WANG KAI, Anhui Medical University

Efficacy and Neural Mechanisms of Neuroimage-guided Dual-target Continuous Theta Burst Stimulation (Auditory Cortex and M1) for Generalized Anxiety Disorder

The purpose of this study is to investigate the effectiveness of a dual-target non-invasive brain stimulation technique called continuous Theta Burst Stimulation (cTBS) for treating Generalized Anxiety Disorder (GAD). The researchers will use a neuronavigation system, which acts like a GPS for the brain, to guide the stimulation to two specific targets: the left auditory association cortex and the primary motor cortex (M1).

Participants will be randomly assigned to one of two groups. One group will receive active dual-target cTBS treatment, while the other will receive a sham (placebo) stimulation that feels similar but has no therapeutic effect. The treatment will be given three times a day for seven consecutive days. Before and after the treatment period, all participants will complete clinical questionnaires to measure their anxiety and undergo Magnetic Resonance Imaging (MRI) scans to help researchers understand how cTBS affects brain activity.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a randomized, triple-blind, sham-controlled trial designed to evaluate the efficacy and neural mechanisms of neuronavigation-guided dual-target continuous Theta Burst Stimulation (cTBS) in patients with Generalized Anxiety Disorder (GAD).

A total of participants diagnosed with GAD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) will be recruited. After providing informed consent, participants will be randomized in a 1:1 ratio to receive either active dual-target cTBS or sham cTBS.

The active intervention involves stimulating two sequential targets using a MagStim Rapid2 stimulator with a 70mm air-cooled figure-of-eight coil:

Target 1 (Auditory Cortex): The first target is the left auditory association cortex (posterior superior temporal sulcus), located using a Brainsight neuronavigation system based on individual MRI scans transformed from MNI coordinates (-62, -40, 10).

Target 2 (M1): The second target is the primary motor cortex (M1), located at the site where the resting motor threshold (RMT) is determined.

Stimulation of the auditory cortex target will be immediately followed by stimulation of the M1 target. The cTBS protocol for each target consists of 3-pulse bursts at 50 Hz, repeated at a 5 Hz frequency, for a total of 600 pulses (40 seconds duration) per target. The stimulation intensity will be set at 100% of the individual's RMT. To achieve cumulative aftereffects, this dual-target protocol will be repeated three times per day with 15-minute intervals between sessions, for seven consecutive days.

The sham intervention will utilize an identical-looking sham coil that produces similar sounds and scalp sensations without inducing a significant magnetic field. The procedure, including neuronavigation, coil placement, and duration, is identical to the active group to maintain the triple-blind design (masking for participants, investigators, and outcomes assessors).

All participants will undergo comprehensive assessments at baseline, post-intervention, and follow-up. Assessments include clinical scales such as the Hamilton Anxiety Rating Scale (HAMA) and multimodal MRI (structural, rs-fMRI, and DTI) to examine neural network dynamics.

Study Type

Interventional

Enrollment (Estimated)

60

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

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230000
        • Anhui Medical University
        • 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

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosis of Generalized Anxiety Disorder (GAD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), confirmed by at least two psychiatrists.
  2. Hamilton Anxiety Rating Scale (HAMA) score > 14.
  3. Age between 18 and 60 years.
  4. Right-handed.
  5. More than 5 years of education.
  6. Patients are either medication-free or maintain a consistent medication regimen during cTBS treatment.
  7. Willing and able to provide written informed consent.
  8. Normal or corrected-to-normal visual acuity and hearing.

Exclusion Criteria:

  1. Presence of other psychiatric disorders, such as substance abuse, schizophrenia, schizoaffective disorder, hysteria, autism, or bipolar disorder.
  2. History of epilepsy, seizures, or severe neurological diseases (e.g., stroke, organic brain lesions).
  3. Presence of severe somatic diseases, such as severe heart, liver, or renal insufficiency.
  4. Pregnant or lactating women.
  5. Contraindications to Transcranial Magnetic Stimulation (TMS) or Magnetic Resonance Imaging (MRI), such as the presence of a cardiac pacemaker, cochlear implant, cerebrovascular metal stent, or metal dentures.
  6. Inability to cooperate with experimental procedures due to conditions such as severe claustrophobia.

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: Active Dual-target cTBS
Participants will receive active continuous Theta Burst Stimulation (cTBS) guided by a neuronavigation system. The stimulation targets are the left auditory association cortex followed by the primary motor cortex (M1). Treatment will be administered three times a day for seven consecutive days.
Device: Active Dual-target cTBS

A non-invasive brain stimulation technique using a MagStim Rapid2 stimulator with a 70mm air-cooled figure-of-eight coil.

Targets: 1. Left auditory association cortex (MNI: -62, -40, 10), located using Brainsight neuronavigation. 2. Primary Motor Cortex (M1), determined by the resting motor threshold (RMT) hotspot. Protocol: Stimulation of the auditory cortex is immediately followed by M1 stimulation. Each target receives a standard cTBS protocol (3-pulse 50 Hz bursts repeated at 5 Hz, total 600 pulses, 40s duration). Dosing: Delivered at 100% RMT. Sessions are repeated 3 times/day with 15-min intervals for 7 days.
Sham Comparator: Sham Dual-target cTBS
Participants will undergo a sham cTBS procedure using a placebo coil. The procedure mimics the sound, sensation, and coil placement (dual-target) of the active group but delivers no effective magnetic field.
Device: Sham Dual-target cTBS
A placebo procedure using an inert sham coil that is identical in appearance and sound to the active coil but does not deliver a significant magnetic field to the cortex. Blinding: The procedure includes identical neuronavigation setup, dual-target coil positioning (Auditory Cortex then M1), duration, and treatment schedule (3 times/day for 7 days) to maintain the blind.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Hamilton Anxiety Rating Scale (HAMA) Score
Time Frame: Baseline (Day 1), Post-intervention (Day 9), and 2-week Follow-up
The HAMA is a 14-item, clinician-administered scale used to assess the severity of anxiety symptoms. Total scores range from 0 to 56, with higher scores indicating more severe anxiety. The change in total score from baseline to post-intervention and follow-up will be assessed.
Baseline (Day 1), Post-intervention (Day 9), and 2-week Follow-up
Change from Baseline in Resting-State Neural Activity
Time Frame: Baseline (Day 1) and Post-intervention (Day 9)
Changes in resting-state brain activity will be measured by functional magnetic resonance imaging (fMRI). Analyses will examine neural activity (ALFF/ReHo) and functional connectivity dynamics related to the stimulation targets (left auditory cortex and M1) and brain circuits implicated in anxiety.
Baseline (Day 1) and Post-intervention (Day 9)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Hamilton Depression Rating Scale (HAMD-17) Score
Time Frame: Baseline (Day 1) and Post-intervention (Day 9)
The HAMD-17 is a 17-item, clinician-rated scale to assess the severity of depression. Total scores range from 0 to 52, with higher scores indicating more severe depression.
Baseline (Day 1) and Post-intervention (Day 9)
Change from Baseline in Self-Rating Anxiety Scale (SAS) Score
Time Frame: Baseline (Day 1), Post-intervention (Day 9), and 2-week Follow-up
The SAS is a 20-item self-report scale designed to measure the severity of anxiety symptoms. The standard score ranges from 25 to 100, where higher scores indicate more severe levels of anxiety.
Baseline (Day 1), Post-intervention (Day 9), and 2-week Follow-up
Change from Baseline in Patient Health Questionnaire-15 (PHQ-15) Score
Time Frame: Baseline (Day 1) and Post-intervention (Day 9)
The PHQ-15 is a 15-item self-report scale to assess the severity of somatic symptoms. Total scores range from 0 to 30, with higher scores indicating more severe somatic symptoms.
Baseline (Day 1) and Post-intervention (Day 9)
Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Score
Time Frame: Baseline (Day 1) and Post-intervention (Day 9)
The PSQI is a self-report questionnaire assessing sleep quality. The global score ranges from 0 to 21, with higher scores indicating worse sleep quality.
Baseline (Day 1) and Post-intervention (Day 9)

Collaborators and Investigators

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

Sponsor

Anhui Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

March 1, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

February 4, 2026

First Submitted That Met QC Criteria

February 4, 2026

First Posted (Actual)

February 11, 2026

Study Record Updates

Last Update Posted (Actual)

February 11, 2026

Last Update Submitted That Met QC Criteria

February 4, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AHMU-GAD-Dual-ACM1-2026

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

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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