Generalized Anxiety Disorder (GAD)NCT07640945
MRI-Guided Accelerated cTBS for Generalized Anxiety Disorder
A study testing continuous theta burst stimulation(cTBS) in people with Generalized Anxiety Disorder (GAD), run by Central South University.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Generalized Anxiety Disorder (GAD)
- What is being tested?
- continuous theta burst stimulation(cTBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- No sites listed yet
- Study dates
- Jun 2026to Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Jing Yang contact
About this study
Official title: Efficacy and Neural Mechanisms of MRI-Guided Accelerated Continuous Theta Burst Stimulation Targeting the Inferior Parietal Lobule in Generalized Anxiety Disorder: A Randomized Controlled Trial
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.
Read the detailed description
Generalized Anxiety Disorder (GAD) is one of the most prevalent psychiatric disorders worldwide and is characterized by excessive and persistent anxiety, impaired psychosocial functioning, and reduced quality of life. Despite the availability of pharmacological and psychological treatments, a substantial proportion of patients continue to experience clinically significant symptoms. Pharmacological therapies often require several weeks before therapeutic benefits emerge, while access to evidence-based psychotherapies remains limited in many settings. Therefore, there is a critical need for novel interventions capable of producing rapid and durable anxiolytic effects.
Transcranial magnetic stimulation (TMS) has emerged as a promising non-invasive neuromodulation technique for the treatment of psychiatric disorders. Continuous theta-burst stimulation (cTBS), a patterned form of repetitive TMS, substantially reduces treatment duration while maintaining efficacy and safety comparable to conventional repetitive TMS protocols. Previous studies have demonstrated therapeutic benefits of cTBS in patients with anxiety disorders; however, conventional treatment courses typically extend over several weeks and may not achieve rapid symptom relief. Accelerated stimulation protocols involving multiple daily treatment sessions over a short period have shown encouraging clinical effects in other psychiatric populations, suggesting potential applicability to anxiety disorders.
Neuroimaging studies have identified the right intraparietal sulcus (IPS) as a key cortical region involved in attentional control, vigilance, salience processing, and anxiety-related arousal. Functional interactions between the IPS and the amygdala are thought to play an important role in regulating emotional and anxiety-related processes. Individual variability in these neural circuits may contribute to heterogeneity in treatment response. Consequently, personalized stimulation targeting based on functional neuroimaging may improve therapeutic outcomes compared with conventional fixed-target approaches.
The present study aims to investigate the efficacy and safety of precision-targeted accelerated cTBS guided by individualized IPS-amygdala functional connectivity in patients with GAD and to explore potential neurobiological mechanisms underlying treatment response. Participants who meet ICD-11 diagnostic criteria for GAD will be randomly assigned in a 1:1:1 ratio to one of three intervention groups: a precision cTBS group, a non-precision cTBS group, or a sham stimulation group.
All participants will receive accelerated cTBS treatment for 5 consecutive days, with five stimulation sessions per day. Each session will deliver 1800 pulses, resulting in a total of 9000 pulses per day, with 50-minute intervals between sessions. Stimulation intensity will be set at 80%-120% of the resting motor threshold. In the precision cTBS group, baseline functional MRI data will be used to identify the right IPS coordinate exhibiting the strongest functional connectivity with the right basolateral amygdala (BLA), and stimulation will be delivered using neuronavigation-guided targeting. In the non-precision cTBS group, stimulation will target a fixed right parietal cortical projection coordinate corresponding to the P4 site reported in previous cranio-cerebral correlation studies of the international 10-20 EEG system. Participants in the sham group will undergo identical procedures using a sham coil.
The primary outcome measure is the change in the total score of the Hamilton Anxiety Rating Scale (HAMA) from baseline to day 5. Secondary outcomes include clinical response and remission rates, changes in relevant clinical symptoms, adverse events occurring during treatment, and neuroimaging indicators. Assessments will be conducted at baseline, during treatment, and at week 2, month 1, and month 2 from baseline to evaluate short-term and sustained treatment effects.
- Conditions
- Generalized Anxiety Disorder (GAD)
- Being tested
- continuous theta burst stimulation(cTBS)
- Keywords
- Generalized Anxiety Disorder (GAD), transcranial magnetic stimulation, Single-center, Randomized Controlled Trial, Non-invasive brain stimulation, Neuromodulation, theta burst stimulation
- Medical subject headings
- Generalized Anxiety Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Device: continuous theta burst stimulation(cTBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Day 5 (End of Treatment)
Secondary outcomes (21)
Clinical Response Rate
Clinical response 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. Clinical response is defined as a reduction of at least 50% in HAMA total score compared with baseline.
Measured: Day 3, Day 5, Week 2, Month 1, and Month 2 from baseline
Clinical Remission Rate
Clinical remission 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. Clinical remission is defined as a HAMA total score of 7 or less at the corresponding assessment time point.
Measured: Day 3 , Day 5 , Week 2, Month 1, and Month 2 from baseline
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline
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 each post-baseline assessment time point.
Measured: Baseline, Day 3, Week 2, Month 1, and Month 2
Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score From Baseline
Depressive symptom severity will be assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), a clinician-administered scale with a total score range of 0 to 52. Higher scores indicate greater depressive symptom severity, which represents a worse outcome. The outcome will be calculated as the change in HAMD-17 total score from baseline to each post-baseline assessment time point.
Measured: 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
Suicidal ideation will be assessed using the Beck Scale for Suicide Ideation (BSI), a 19-item scale with a total score range of 0 to 38. Higher scores indicate more severe suicidal ideation, which represents a worse outcome. The outcome will be calculated as the change in BSI score from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Generalized Anxiety Disorder-7 (GAD-7) Score From Baseline
Anxiety symptom severity will be assessed using the Generalized Anxiety Disorder-7 (GAD-7), a 7-item self-report questionnaire with a total score range of 0 to 21. Higher scores indicate greater anxiety symptom severity, which represents a worse outcome. The outcome will be calculated as the change in GAD-7 score from baseline to each post-baseline assessment time point.
Measured: Baseline, Day 3, Day 5, Week 2 and Month 1 from baseline
Change in Patient Health Questionnaire-15 (PHQ-15) Score From Baseline
Somatic symptom severity will be assessed using the Patient Health Questionnaire-15 (PHQ-15), a 15-item self-report questionnaire with a total score range of 0 to 30. Higher scores indicate greater somatic symptom severity, which represents a worse outcome. The outcome will be calculated as the change in PHQ-15 score from baseline to each post-baseline assessment time point.
Measured: Baseline, Day 3, Day 5, Week 2 and Month 1 from baseline
Change in Patient Health Questionnaire-9 (PHQ-9) Score From Baseline
Depressive symptom severity will be assessed using the Patient Health Questionnaire-9 (PHQ-9), a 9-item self-report questionnaire with a total score range of 0 to 27. Higher scores indicate greater depressive symptom severity, which represents a worse outcome. The outcome will be calculated as the change in PHQ-9 score from baseline to each post-baseline assessment time point.
Measured: Baseline, Day 3, Day 5, Week 2 and Month 1 from baseline
Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline
Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a self-report questionnaire with a global score range of 0 to 21. Higher scores indicate poorer sleep quality, which represents a worse outcome. The outcome will be calculated as the change in PSQI global score from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Penn State Worry Questionnaire (PSWQ) Score From Baseline
Worry severity will be assessed using the Penn State Worry Questionnaire (PSWQ), a 16-item self-report questionnaire with a total score range of 16 to 80. Higher scores indicate greater worry severity, which represents a worse outcome. The outcome will be calculated as the change in PSWQ score from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Intolerance of Uncertainty Scale (IUS) Score From Baseline
Intolerance of uncertainty will be assessed using the Intolerance of Uncertainty Scale (IUS), a 27-item self-report questionnaire with a total score range of 27 to 135. Higher scores indicate greater intolerance of uncertainty, which represents a worse outcome. The outcome will be calculated as the change in IUS score from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Cognitive Test Performance From Baseline to Day 5
Cognitive function will be assessed using neurocognitive tests administered in this study. The score range depends on the specific cognitive test or task. For accuracy-based cognitive measures, higher scores indicate better cognitive performance, which represents a better outcome; for time-based measures such as reaction time, higher values indicate slower performance, which represents a worse outcome. The outcome will be calculated as the change in cognitive test performance from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in State-Trait Anxiety Inventory (STAI) Score From Baseline
Anxiety symptoms and anxiety proneness will be assessed using the State-Trait Anxiety Inventory (STAI), a 40-item self-report questionnaire consisting of the State Anxiety and Trait Anxiety subscales. Each subscale has a score range of 20 to 80. Higher scores indicate greater anxiety, which represents a worse outcome. The outcome will be calculated as the change in STAI score from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Perceived Stress Scale-10 (PSS-10) Score From Baseline
Perceived stress will be assessed using the Perceived Stress Scale-10 (PSS-10), a 10-item self-report questionnaire with a total score range of 0 to 40. Higher scores indicate higher perceived stress, which represents a worse outcome. The outcome will be calculated as the change in PSS-10 score from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Ruminative Responses Scale (RRS) Score From Baseline
Rumination will be assessed using the Ruminative Responses Scale (RRS), a 22-item self-report questionnaire with a total score range of 22 to 88. Higher scores indicate greater rumination, which represents a worse outcome. The outcome will be calculated as the change in RRS score from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Anxiety and Depression Visual Analogue Scale Scores From Baseline
Subjective anxiety and depression severity will be assessed using visual analogue scale ratings for anxiety and depression. Each visual analogue scale score ranges from 0 to 10, with higher scores indicating greater subjective symptom severity, which represents a worse outcome. The outcome will be calculated as the change in visual analogue scale scores from baseline to each post-baseline assessment time point.
Measured: Baseline, Day 1, Day 3, Day 5 and Week 2 from baseline
Treatment-Emergent Side Effects During the Intervention and Follow-up Period
Treatment-emergent side effects will be assessed using a physical treatment side-effect assessment that records the presence, type, severity, and relationship to the study intervention of adverse events. This outcome will be summarized as the occurrence and severity of treatment-emergent side effects during the intervention and follow-up period; higher severity indicates a worse safety outcome.
Measured: Day 1, Day 3, Day 5 and Week 2 from baseline
Change in Heart Rate Variability From Baseline to Day 5
Heart rate variability will be assessed to evaluate autonomic nervous system function. Heart rate variability parameters may include time-domain and frequency-domain measures such as the standard deviation of normal-to-normal intervals and the root mean square of successive differences. The expected range depends on the specific heart rate variability parameter. In general, higher heart rate variability reflects better autonomic flexibility and may represent a better physiological outcome. The outcome will be calculated as the change in heart rate variability measures from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Change in Magnetic Resonance Imaging Measures From Baseline to Day 5
Brain structural and/or functional measures will be assessed using magnetic resonance imaging. The specific values and ranges depend on the imaging modality and derived measure, such as structural, functional connectivity, or brain network metrics. Interpretation will depend on the specific magnetic resonance imaging measure analyzed. The outcome will be calculated as the change in magnetic resonance imaging measures from baseline to Day 5.
Measured: Baseline and Day 5 (End of Treatment)
Dysfunctional Attitudes Scale (DAS) Score at Baseline
Dysfunctional attitudes will be assessed using the Dysfunctional Attitudes Scale (DAS), a 40-item self-report scale with a total score range of 40 to 280. Higher scores indicate more dysfunctional attitudes, which represents a worse psychological profile. This measure will be assessed at baseline.
Measured: Baseline
Childhood Trauma Questionnaire (CTQ) Score at Baseline
Childhood trauma exposure will be assessed using the Childhood Trauma Questionnaire (CTQ), a 25-item self-report questionnaire with a total score range of 25 to 125. Higher scores indicate greater childhood trauma exposure, which represents a worse psychosocial profile. This measure will be assessed at baseline.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2026
- Study startJun 2026 (estimated)
- Primary completionJan 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Generalized Anxiety Disorder (GAD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central South University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yumeng Ju, Central South University
- Investigators
- Yan Zhang, PhD, Study chair, Second Xiangya Hospital of Central South UniversityYumeng Ju, PhD, Principal investigator, Second Xiangya Hospital of Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07640945
- Sponsor's protocol ID
- KYZ20240157
- Status last verified
- Jun 2026
- First submitted
- 28 May 2026
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Neural Mechanisms of MRI-Guided Accelerated Continuous Theta Burst Stimulation Targeting the Inferior Parietal Lobule in Generalized Anxiety Disorder: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07640945
- Acronym / sponsor ID
- KYZ20240157
- 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
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Central South UniversityUniversity, hospital or other
- Study start
- Jun 2026 (estimated)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 11 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Generalized Anxiety Disorder (GAD) is one of the most prevalent psychiatric disorders worldwide and is characterized by excessive and persistent anxiety, impaired psychosocial functioning, and reduced quality of life. Despite the availability of pharmacological and psychological treatments, a substantial proportion of patients continue to experience clinically significant symptoms. Pharmacological therapies often require several weeks before therapeutic benefits emerge, while access to evidence-based psychotherapies remains limited in many settings. Therefore, there is a critical need for novel interventions capable of producing rapid and durable anxiolytic effects.
Transcranial magnetic stimulation (TMS) has emerged as a promising non-invasive neuromodulation technique for the treatment of psychiatric disorders. Continuous theta-burst stimulation (cTBS), a patterned form of repetitive TMS, substantially reduces treatment duration while maintaining efficacy and safety comparable to conventional repetitive TMS protocols. Previous studies have demonstrated therapeutic benefits of cTBS in patients with anxiety disorders; however, conventional treatment courses typically extend over several weeks and may not achieve rapid symptom relief. Accelerated stimulation protocols involving multiple daily treatment sessions over a short period have shown encouraging clinical effects in other psychiatric populations, suggesting potential applicability to anxiety disorders.
Neuroimaging studies have identified the right intraparietal sulcus (IPS) as a key cortical region involved in attentional control, vigilance, salience processing, and anxiety-related arousal. Functional interactions between the IPS and the amygdala are thought to play an important role in regulating emotional and anxiety-related processes. Individual variability in these neural circuits may contribute to heterogeneity in treatment response. Consequently, personalized stimulation targeting based on functional neuroimaging may improve therapeutic outcomes compared with conventional fixed-target approaches.
The present study aims to investigate the efficacy and safety of precision-targeted accelerated cTBS guided by individualized IPS-amygdala functional connectivity in patients with GAD and to explore potential neurobiological mechanisms underlying treatment response. Participants who meet ICD-11 diagnostic criteria for GAD will be randomly assigned in a 1:1:1 ratio to one of three intervention groups: a precision cTBS group, a non-precision cTBS group, or a sham stimulation group.
All participants will receive accelerated cTBS treatment for 5 consecutive days, with five stimulation sessions per day. Each session will deliver 1800 pulses, resulting in a total of 9000 pulses per day, with 50-minute intervals between sessions. Stimulation intensity will be set at 80%-120% of the resting motor threshold. In the precision cTBS group, baseline functional MRI data will be used to identify the right IPS coordinate exhibiting the strongest functional connectivity with the right basolateral amygdala (BLA), and stimulation will be delivered using neuronavigation-guided targeting. In the non-precision cTBS group, stimulation will target a fixed right parietal cortical projection coordinate corresponding to the P4 site reported in previous cranio-cerebral correlation studies of the international 10-20 EEG system. Participants in the sham group will undergo identical procedures using a sham coil.
The primary outcome measure is the change in the total score of the Hamilton Anxiety Rating Scale (HAMA) from baseline to day 5. Secondary outcomes include clinical response and remission rates, changes in relevant clinical symptoms, adverse events occurring during treatment, and neuroimaging indicators. Assessments will be conducted at baseline, during treatment, and at week 2, month 1, and month 2 from baseline to evaluate short-term and sustained treatment effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Precision cTBS stimulation group | Experimental | Device: continuous theta burst stimulation(cTBS)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. |
| Non-precise cTBS stimulation group | Experimental | Device: continuous theta burst stimulation(cTBS)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. |
| Sham stimulation group | Sham comparator | Device: continuous theta burst stimulation(cTBS)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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| continuous theta burst stimulation(cTBS)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. | Device | Non-precise cTBS stimulation group, Precision cTBS stimulation group, Sham stimulation group |
Primary outcome
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Day 5
Time frame: Baseline and Day 5 (End of Treatment)
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.
21 secondary outcomes
Clinical Response Rate
Time frame: Day 3, Day 5, Week 2, Month 1, and Month 2 from baseline
Clinical Remission Rate
Time frame: Day 3 , Day 5 , Week 2, Month 1, and Month 2 from baseline
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline
Time frame: Baseline, Day 3, Week 2, Month 1, and Month 2
Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score From Baseline
Time frame: 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
Time frame: Baseline and Day 5 (End of Treatment)
Change in Generalized Anxiety Disorder-7 (GAD-7) Score From Baseline
Time frame: Baseline, Day 3, Day 5, Week 2 and Month 1 from baseline
Change in Patient Health Questionnaire-15 (PHQ-15) Score From Baseline
Time frame: Baseline, Day 3, Day 5, Week 2 and Month 1 from baseline
Change in Patient Health Questionnaire-9 (PHQ-9) Score From Baseline
Time frame: Baseline, Day 3, Day 5, Week 2 and Month 1 from baseline
Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline
Time frame: Baseline and Day 5 (End of Treatment)
Change in Penn State Worry Questionnaire (PSWQ) Score From Baseline
Time frame: Baseline and Day 5 (End of Treatment)
Change in Intolerance of Uncertainty Scale (IUS) Score From Baseline
Time frame: Baseline and Day 5 (End of Treatment)
Change in Cognitive Test Performance From Baseline to Day 5
Time frame: Baseline and Day 5 (End of Treatment)
Change in State-Trait Anxiety Inventory (STAI) Score From Baseline
Time frame: Baseline and Day 5 (End of Treatment)
Change in Perceived Stress Scale-10 (PSS-10) Score From Baseline
Time frame: Baseline and Day 5 (End of Treatment)
Change in Ruminative Responses Scale (RRS) Score From Baseline
Time frame: Baseline and Day 5 (End of Treatment)
Change in Anxiety and Depression Visual Analogue Scale Scores From Baseline
Time frame: Baseline, Day 1, Day 3, Day 5 and Week 2 from baseline
Treatment-Emergent Side Effects During the Intervention and Follow-up Period
Time frame: Day 1, Day 3, Day 5 and Week 2 from baseline
Change in Heart Rate Variability From Baseline to Day 5
Time frame: Baseline and Day 5 (End of Treatment)
Change in Magnetic Resonance Imaging Measures From Baseline to Day 5
Time frame: Baseline and Day 5 (End of Treatment)
Dysfunctional Attitudes Scale (DAS) Score at Baseline
Time frame: Baseline
Childhood Trauma Questionnaire (CTQ) Score at Baseline
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Generalized Anxiety Disorder (GAD)
Not yet recruiting
CannaRiver CBD Calm for Anxiety, Sleep, and Well-Being in Adults With Generalized Anxiety Disorder
Generalized Anxiety Disorder
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruitingPhase 1
Microbiota Modulation for Psychiatry Patients
Depression - Major Depressive Disorder, Generalized Anxiety Disorder (GAD)
Recruiting
Electroacupuncture for Generalized Anxiety Disorder: Clinical Efficacy and Neuroimaging Mechanisms
Generalized Anxiety Disorder
RecruitingPhase 3
A Trial of the Efficacy and Safety of Fixed Doses of SEP-363856 in Adults With Generalized Anxiety Disorder
Generalized Anxiety Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jing Yang contact
Yan Zhang, PhD study chair
Second Xiangya Hospital of Central South University
Yumeng Ju, PhD principal investigator
Second Xiangya Hospital of Central South University
Questions about this trial
What is this clinical trial studying?
A study testing continuous theta burst stimulation(cTBS) in people with Generalized Anxiety Disorder (GAD), run by Central South University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yumeng Ju, PhD (86+18100731091, yumeng.ju@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Day 5 (time frame: Baseline and Day 5 (End of Treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.