Navigated cTBS for the Treatment of Generalized Anxiety Disorder

NCT07121712 | Recruiting

• 1 other identifier: AnHuiMU-GAD-cTBS-2025
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to investigate the effectiveness of a 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 based on a participant's own MRI scan, to guide the stimulation to a specific target in the brain's auditory association cortex. This area is involved in processing information and may play a role in anxiety. Participants who enroll will be randomly assigned to one of two groups. One group will receive active 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 related symptoms. They will also undergo Magnetic Resonance Imaging (MRI) scans to help researchers understand how cTBS affects brain activity. A follow-up assessment will be conducted two weeks after the treatment ends to check on symptoms.

Conditions

Generalized Anxiety Disorder

Keywords

Generalized Anxiety Disorder; Continuous Theta Burst Stimulation; Transcranial Magnetic Stimulation; Neuronavigation; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (3)

• 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 will be

  Baseline (Day 1), Post-intervention (Day 9), and a 2-week follow-up.

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

  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. The change in standard score from baseline will be assessed.

  Baseline (Day 1), Post-intervention (Day 9), and a 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 and network dynamics related to the stimulation target (left auditory cortex) 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 Patient Health Questionnaire-15 (PHQ-15) Score

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

• Change from Baseline in Four-Dimensional Symptom Questionnaire (4DSQ) Somatization Subscale 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)

Experimental: Navigated cTBS

EXPERIMENTAL

Participants will receive active continuous Theta Burst Stimulation (cTBS) guided by a neuronavigation system to the left auditory association cortex. Treatment will be administered three times a day for seven consecutive days.

Device: Mapsd Continuous Theta Burst Stimulation

Sham Comparator: Sham cTBS

SHAM COMPARATOR

Participants will undergo a sham cTBS procedure using a placebo coil that mimics the sound and sensation of the active stimulation but delivers no effective magnetic field. The procedure, including targeting and duration, is identical to the active group to maintain blinding.

Device: Sham Navigated Continuous Theta Burst Stimulation

Interventions

Mapsd Continuous Theta Burst Stimulation DEVICE

A non-invasive brain stimulation technique using a MagStim Rapid2 stimulator with a 70mm air-cooled figure-of-eight coil. The stimulation target is the left auditory association cortex (MNI: -62, -40, 10), located using a Brainsight neuronavigation system. The cTBS protocol consists of 3-pulse 50 Hz bursts repeated at a 5 Hz frequency for a total of 600 pulses, delivered at 100% of the individual's resting motor threshold (RMT).

Experimental: Navigated cTBS

Sham Navigated Continuous Theta Burst Stimulation 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. All other aspects of the procedure, including neuronavigation, coil placement, duration, and sound, are identical to the active intervention to maintain the blind.

Sham Comparator: Sham 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.
• More than 5 years of education.
• Right-handed.
• Normal or corrected-to-normal visual acuity.
• Able to cooperate with the completion of all experimental procedures.
• Willing and able to provide written informed consent.

You may not qualify if:

• Presence of other psychiatric disorders, such as substance abuse, schizophrenia, schizoaffective disorder, hysteria, or autism.
• Presence of severe neurological diseases (e.g., stroke), or any personal or family history of epilepsy or seizures.
• 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 depressive stupor or severe claustrophobia.

Sponsors & Collaborators

• WANG KAI: lead

Study Sites (2)

Anhui Medical University

Hefei, Anhui, 230000, China

RECRUITING

Anhui Medical University

Hefei, Anhui, 230000, China

RECRUITING

Related Publications (2)

• Ji GJ, Ren C, Li Y, Sun J, Liu T, Gao Y, Xue D, Shen L, Cheng W, Zhu C, Tian Y, Hu P, Chen X, Wang K. Regional and network properties of white matter function in Parkinson's disease. Hum Brain Mapp. 2019 Mar;40(4):1253-1263. doi: 10.1002/hbm.24444. Epub 2018 Nov 10.

  PMID: 30414340 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Generalized Anxiety Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Central Study Contacts

Kai Wang, MD

CONTACT

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

Tongjian Bai, MD

CONTACT

baiyunong1990@163.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: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: June 29, 2025
• First Posted: August 13, 2025
• Study Start: September 9, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)