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

NCT07403591 | Not Yet Recruiting

• 1 other identifier: AHMU-GAD-Dual-ACM1-2026
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Generalized Anxiety Disorder

Keywords

Generalized Anxiety Disorder; Continuous Theta Burst Stimulation; Transcranial Magnetic Stimulation; Neuronavigation; Dual-target; Auditory Cortex; Primary Motor Cortex

Outcome Measures

Primary Outcomes (2)

• Change from Baseline in Hamilton Anxiety Rating Scale (HAMA) Score

  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

  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 Outcomes (4)

• Change from Baseline in Hamilton Depression Rating Scale (HAMD-17) Score

  Baseline (Day 1) and Post-intervention (Day 9)

• Change from Baseline in Self-Rating Anxiety Scale (SAS) Score

  Baseline (Day 1), Post-intervention (Day 9), and 2-week Follow-up

• Change from Baseline in Patient Health Questionnaire-15 (PHQ-15) Score

  Baseline (Day 1) and Post-intervention (Day 9)

• Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Score

  Baseline (Day 1) and Post-intervention (Day 9)

Study Arms (2)

Active Dual-target cTBS

EXPERIMENTAL

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

Sham Dual-target cTBS

SHAM COMPARATOR

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

Interventions

Active Dual-target cTBS DEVICE

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.

Active Dual-target cTBS

Sham Dual-target cTBS DEVICE

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.

Sham Dual-target cTBS

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Hamilton Anxiety Rating Scale (HAMA) score \> 14.
• Age between 18 and 60 years.
• Right-handed.
• More than 5 years of education.
• Patients are either medication-free or maintain a consistent medication regimen during cTBS treatment.
• Willing and able to provide written informed consent.
• Normal or corrected-to-normal visual acuity and hearing.

You may not qualify if:

• Presence of other psychiatric disorders, such as substance abuse, schizophrenia, schizoaffective disorder, hysteria, autism, or bipolar disorder.
• History of epilepsy, seizures, or severe neurological diseases (e.g., stroke, organic brain lesions).
• Presence of severe somatic diseases, such as severe heart, liver, or renal insufficiency.
• Pregnant or lactating women.
• 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.
• Inability to cooperate with experimental procedures due to conditions such as severe claustrophobia.

Sponsors & Collaborators

• Anhui Medical University: lead

Study Sites (1)

Anhui Medical University

Hefei, Anhui, 230000, China

Location

Related Publications (1)

• Neri F, Cappello C, Viberti F, Donniacuo A, Burzi L, Cinti A, Benelli A, Luca Smeralda C, Romanella S, Santarnecchi E, Mandala M, Rossi S. rTMS of the auditory association cortex improves speech intelligibility in patients with sensorineural hearing loss. Clin Neurophysiol. 2024 Apr;160:38-46. doi: 10.1016/j.clinph.2024.02.007. Epub 2024 Feb 9.

  PMID: 38395005 RESULT

MeSH Terms

Conditions

Generalized Anxiety Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Central Study Contacts

Kai Wang, PhD

CONTACT

+86-0551-62923704; wangkai1964@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 11, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)