Neuroimage-guided Dual-target Continuous Theta Burst Stimulation for Generalized Anxiety Disorder

NCT ID: NCT06699706

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2025-11-01

Brief Summary

The aim of this clinical trial was to determine whether image-guided dual-target cTBS is effective for anxiety disorders. The main questions it aims to answer are:

1. Does dual-target cTBS improve patients' anxiety symptoms?

2. Does dual-target cTBS improve patients' somatization symptoms?

3. Researchers will compare cTBS real and sham stimulation to determine whether cTBS is effective in treating anxiety disorders.

Participants will:

1. Received either cTBS treatment or sham stimulation for 7 consecutive days

2. Psychological assessment and MRI scan were performed before treatment, within 2 days, 2 weeks and 1 month after treatment

3. Adverse reactions during the experiment were recorded

Detailed Description

This was a randomized, double-blind, sham-controlled clinical trial. Patients with generalized anxiety disorder (GAD) were recruited from the Neurology Outpatient Clinic and Psychiatry Outpatient Clinic at the First Affiliated Hospital of Anhui Medical University, as well as the Psychiatry Outpatient Clinic and Inpatient Ward at the Second Affiliated Hospital of Anhui Medical University. The diagnosis of GAD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), independently confirmed by two professional psychiatrists. Patients meeting the inclusion criteria provided written informed consent and were randomly assigned to either a true cTBS treatment group or a sham stimulation group.

Patients will be randomly assigned to receive either active or sham cTBS treatments according to a computer-generated list by an unblinded investigator not involved with study ratings/analysis. The assignment will be executed by utilizing sealed opaque envelopes, each containing the code corresponding to the assigned group for every participant. To ensure the integrity of the double-blind procedure, patients, clinical raters, and all personnel responsible for the clinical care of patients will remain uninformed about the assigned condition until the end point of study. Only cTBS administrators have access to the randomization list. The patients, clinical assessors, and all personnel responsible for clinical care remained blinded to group allocation.

After randomization, patients underwent 7 days of cTBS treatment and completed psychological evaluations and multimodal MRI scans at three time points: baseline, post-treatment, and follow-up. Baseline evaluations were conducted within 24 hours before the first cTBS session, while post-treatment and follow-up evaluations were performed 24 hours after the final cTBS session and four weeks later, respectively.

At each time point (baseline, post-treatment, and follow-up), trained evaluators conducted MRI scans and administered the following scales and behavioral paradigms:

Hamilton Anxiety Rating Scale (HAMA); Hamilton Depression Rating Scale (HAMD); Patient Health Questionnaire-15 (PHQ-15); Self-Rating Anxiety Scale (SAS); Insomnia Severity Index (ISI); MFTM-A (Cognitive Control Capacity); Attention Network Test (ANT).

These scales and paradigms were used to assess the severity of symptoms across different dimensions of anxiety. Additionally, demographic data, structural MRI (sMRI), and functional MRI (fMRI) data were collected at baseline. The sMRI data were utilized for real-time navigation during stimulation.

Conditions

Anxiety; Transcranial Magnetic Stimulation Repetitive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

active cTBS group

Dual-target active cTBS will be performed over 7 consecutive days

Group Type: ACTIVE_COMPARATOR

Continuous theta-burst stimulation

Intervention Type: OTHER

cTBS targets two regions: the dorsolateral prefrontal cortex (dlPFC) and the M1 area. Before the first treatment, each participant's resting motor threshold (RMT) will be determined using a five-step procedure for the primary motor cortex. RMT is defined as the minimum intensity required to elicit a motor response greater than 50 µV in at least 5 out of 10 consecutive trials in the right first dorsal interosseous muscle.

Participants will then undergo daily cTBS treatment three times a day for 7 consecutive days. Each stimulation session lasts 40 seconds, consisting of triplets of 50 Hz theta-burst stimulation repeated at 5 Hz, delivering a total of 600 pulses. Stimulation of the dlPFC target will be immediately followed by stimulation of the M1 target. To achieve cumulative aftereffects, the protocol will be repeated three times per day (a total of 3600 pulses/day) with two 15-minute breaks between sessions, timed with a stopwatch.

sham cTBS group

Sham stimulation of dual-target cTBS was performed for 7 consecutive days using a sham coil

Group Type: SHAM_COMPARATOR

sham continuous theta-burst stimulation

Intervention Type: OTHER

The treatment pattern for the sham continuous theta-burst stimulation was similar to that for real stimulation. The sham coil is identical in appearance to the active coil, but it only produces sounds and sensations similar to those of the active coil on the scalp without generating a current, preventing participants from identifying their group assignment.

Interventions

Continuous theta-burst stimulation

cTBS targets two regions: the dorsolateral prefrontal cortex (dlPFC) and the M1 area. Before the first treatment, each participant's resting motor threshold (RMT) will be determined using a five-step procedure for the primary motor cortex. RMT is defined as the minimum intensity required to elicit a motor response greater than 50 µV in at least 5 out of 10 consecutive trials in the right first dorsal interosseous muscle.

Participants will then undergo daily cTBS treatment three times a day for 7 consecutive days. Each stimulation session lasts 40 seconds, consisting of triplets of 50 Hz theta-burst stimulation repeated at 5 Hz, delivering a total of 600 pulses. Stimulation of the dlPFC target will be immediately followed by stimulation of the M1 target. To achieve cumulative aftereffects, the protocol will be repeated three times per day (a total of 3600 pulses/day) with two 15-minute breaks between sessions, timed with a stopwatch.

Intervention Type: OTHER

sham continuous theta-burst stimulation

The treatment pattern for the sham continuous theta-burst stimulation was similar to that for real stimulation. The sham coil is identical in appearance to the active coil, but it only produces sounds and sensations similar to those of the active coil on the scalp without generating a current, preventing participants from identifying their group assignment.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. the patients were diagnosed by more than 2 psychiatrists and met the diagnostic criteria of DSM-5 for anxiety

2. HAMA score ≥ 14 (HAMD score < 17).

3. Age range: 18-60 years.

4. Right-handed.

5. Able to cooperate with the collection of general demographic information and neuropsychological testing.

6. Patients are either medication-free or maintain a consistent medication regimen during cTBS treatment.-

Exclusion Criteria

1. Presence of organic brain lesions detected on MRI.

2. History of alcohol or drug dependence.

3. Diagnosis of other neuropsychiatric disorders, such as epilepsy, autism, obsessive-compulsive disorder, or autoimmune encephalitis.

4. Contraindications to MRI scanning.-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Anhui Medical University

OTHER

Sponsor Role: lead

Responsible Party

WANG KAI

phD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Cognitive Neuropsychology Lab Anhui Medical University

Hefei, Anhui, China

Countries

China

Other Identifiers

AHMU-cTBS-anxiety

Identifier Type: -

Identifier Source: org_study_id