MRI-Guided Accelerated cTBS for Generalized Anxiety Disorder

NCT07640945 | Not Yet Recruiting

• 1 other identifier: KYZ20240157
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

Generalized Anxiety Disorder (GAD) is a common psychiatric disorder associated with persistent anxiety, functional impairment, and incomplete response to existing treatments. Although transcranial magnetic stimulation (TMS) has shown therapeutic potential in anxiety disorders, conventional treatment schedules often require several weeks and may not provide sufficiently rapid symptom relief. This study aims to evaluate the efficacy and safety of precision-targeted accelerated continuous theta-burst stimulation (cTBS) guided by individualized functional connectivity between the intraparietal sulcus (IPS) and the amygdala in patients with GAD.

Conditions

Generalized Anxiety Disorder (GAD)

Keywords

Generalized Anxiety Disorder (GAD); transcranial magnetic stimulation; Single-center; Randomized Controlled Trial; Non-invasive brain stimulation; Neuromodulation; theta burst stimulation

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Day 5

  Anxiety symptom severity will be assessed using the Hamilton Anxiety Rating Scale (HAMA), a 14-item clinician-administered scale with a total score range of 0 to 56. Higher scores indicate greater anxiety symptom severity, which represents a worse outcome. The outcome will be calculated as the change in HAMA total score from baseline to Day 5.

  Baseline and Day 5 (End of Treatment)

Secondary Outcomes (21)

• Clinical Response Rate

  Day 3, Day 5, Week 2, Month 1, and Month 2 from baseline

• Clinical Remission Rate

  Day 3 , Day 5 , Week 2, Month 1, and Month 2 from baseline

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

  Baseline, Day 3, Week 2, Month 1, and Month 2

• Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score From Baseline

  Baseline, Day 3, Day 5, Week 2, Month 1, and Month 2 from baseline

• Change in Beck Scale for Suicide Ideation (BSI) Score From Baseline

  Baseline and Day 5 (End of Treatment)

Study Arms (3)

Precision cTBS stimulation group

EXPERIMENTAL

Undergo precise targeted accelerated cTBS guided by individual right IPS-right BLA functional connectivity. The individual IPS target is located using the Visor2 neuronavigation system, with treatment administered continuously for 5 days, 5 times per day, each session lasting 120 seconds with 1800 pulses, and an interval of 50 minutes between sessions.

Device: continuous theta burst stimulation(cTBS)

Non-precise cTBS stimulation group

EXPERIMENTAL

Receive non-individualised target cTBS. Use the cortical target corresponding to the P4 site of the international 10-20 EEG system as the stimulation target, with the remaining equipment, stimulation intensity, frequency, treatment course, number of pulses per session, and treatment procedures consistent with the precise cTBS group.

Device: continuous theta burst stimulation(cTBS)

Sham stimulation group

SHAM COMPARATOR

Receive sham cTBS. Apart from using a sham coil with no effective magnetic field output, the coil placement, neuronavigation procedure, number of treatments, treatment duration, and follow-up process are consistent with the precise cTBS group.

Device: continuous theta burst stimulation(cTBS)

Interventions

continuous theta burst stimulation(cTBS) DEVICE

Accelerated cTBS treatment was administered over 5 days, five times daily (1800 pulses per session, a total of 9000 pulses per day, with 50-minute intervals between sessions), at a stimulation intensity of 80%-120% of the resting motor threshold. The precise stimulation group targeted locations based on individual baseline functional MRI data, calculating the coordinates of strongest functional connectivity between the right IPS and the right basolateral amygdala (BLA), and implemented via neuronavigation system registration; the non-precise stimulation group targeted the cortical projection coordinates of the P4 electrode site according to the international 10-20 EEG system; the sham stimulation group used the same parameters but with a sham coil.

Non-precise cTBS stimulation group; Precision cTBS stimulation group; Sham stimulation group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatients or inpatients at the Second Xiangya Hospital who are confirmed by two experienced psychiatrists to meet the International Classification of Diseases 11th Revision (ICD-11) diagnostic criteria for generalized anxiety disorder.
• Aged 18 to 65 years, regardless of gender.
• Right-handed.
• Junior high school education or above, with the ability to provide informed consent and complete cognitive assessments.
• Able to receive anti-anxiety treatment during the follow-up period according to the instructions of outpatient or inpatient physicians.
• Hamilton Anxiety Rating Scale (HAMA) score ≥14 and Patient Health Questionnaire-15 (PHQ-15) score ≥5.

You may not qualify if:

• Presence of psychotic symptoms.
• Diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, current psychiatric symptoms, or post-traumatic stress disorder based on SCID-5 assessment, either currently or within the past year.
• Organic brain disease or severe somatic diseases, such as thyroid disease, lupus, diabetes, lung disease, liver disease, kidney disease, infection, or major trauma.
• Intracranial implants.
• Clinically significant sensory impairments that cannot be corrected, such as color blindness or hearing impairment.
• Pregnant or breastfeeding women.
• Positive urine drug screen.
• Abnormal thyroid function tests.
• Personal history of epilepsy or family history of epilepsy.
• Receipt of physical therapy within the past six months, such as repetitive transcranial magnetic stimulation or electroconvulsive therapy.
• Suspected or confirmed history of alcohol or drug dependence.
• Use of anticoagulants, such as heparin or warfarin, corticosteroids, or thyroid disease treatments within the past three months.
• Current use of psychoactive medications.
• Receipt of neurocognitive assessments similar to those used in this study within the past 12 months.

Sponsors & Collaborators

• Central South University: lead

MeSH Terms

Conditions

Generalized Anxiety Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Study Officials

• Yan Zhang, PhD

  Second Xiangya Hospital of Central South University

  STUDY CHAIR

• Yumeng Ju, PhD

  Second Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yumeng Ju, PhD

CONTACT

86+18100731091; yumeng.ju@csu.edu.cn

Jing Yang

CONTACT

yangjing2025@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study adopts a randomised, quadruple-blind, sham-controlled design. Eligible patients with generalized anxiety disorder who provide written informed consent will be randomly assigned in a 1:1:1 ratio to the precise cTBS stimulation group, non-precise cTBS stimulation group, or sham stimulation group using an R-generated random sequence prepared by an independent statistician not involved in treatment, intervention delivery, outcome assessment, or data analysis. Participants, care providers, investigators, and outcome assessors will be blinded to group allocation. Stimulation will be administered by designated unblinded personnel who will not participate in clinical care, assessments, or data analysis. To maintain blinding, all groups will receive 5 days of accelerated cTBS, with five sessions per day, and comparable stimulation procedures, session duration, inter-session intervals, and follow-up assessments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Investigator

Model Details: The precise cTBS group calculates the IPS coordinates with the strongest functional connectivity to the right basolateral amygdala (BLA) based on individual baseline MRI data, and after correction with individual structural images and spatial deformation fields, imports them into the neuronavigation system as stimulation targets; the non-precise cTBS group uses the P4 electrode position of the international 10-20 EEG system as the stimulation target, and after registration to individual structural images through the neuronavigation system, stimulation is carried out; the sham stimulation group follows the same treatment protocol, device appearance, coil placement and neuronavigation procedure, but uses a sham coil and does not provide effective cortical stimulation. All three groups undergo a 5-day accelerated cTBS intervention, with 5 sessions per day, maintaining consistent stimulation parameters, treatment duration, inter-treatment intervals, and follow-up assessment procedures.

Study Record Dates

• First Submitted: May 28, 2026
• First Posted: June 11, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share