NCT07466277

Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Social Anxiety Disorder

Intermittent Theta-Burst Stimulation Targeting the Prefrontal Cortex for Social Anxiety Disorder: A Randomized, Parallel-Group Comparative Study

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 16 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This study aims to investigate the therapeutic effects of intermittent theta burst stimulation on social anxiety disorder and to track physiological changes in the brain using electroencephalography (EEG). Eligible SAD participants, after voluntarily signing an informed consent form, will first complete basic information collection, baseline questionnaire completion, and a pre-treatment EEG data collection session lasting approximately 30 minutes (including resting-state and task-state recordings). Subsequently, participants will be randomly assigned to one of three groups (left iTBS group, right iTBS group, or sham stimulation group) to receive intensive treatment for one week (4 sessions daily for 5 consecutive days, totaling 20 sessions). Immediately following the intervention, the research team will conduct post-treatment EEG data collection and gather questionnaire assessments. Participants will also undergo follow-up visits at weeks 2, 4, 6, and 8 post-treatment to complete questionnaires and report any adverse events. All study procedures are strictly and safely conducted by trained professionals. Participation is entirely voluntary, and participants may withdraw unconditionally at any time during the study.

Detailed description

Social Anxiety Disorder (SAD) is a disabling psychiatric disorder characterized by intense fear and avoidance behaviors in social situations. Current pharmacological and psychological treatments are limited by insufficient response rates and a delayed onset of action. Intermittent theta-burst stimulation (iTBS), a novel non-invasive neuromodulation technique, offers advantages such as shorter stimulation duration and better tolerability; however, its precise targeting and clinical efficacy in SAD require high-quality evidence from randomized controlled trials (RCTs). This study aims to conduct a randomized, double-blind, sham-controlled clinical trial to investigate the clinical efficacy of an intensive iTBS protocol targeting the prefrontal cortex (PFC) in patients with SAD. Concurrently, the study will utilize electroencephalography (EEG) to objectively record participants' neurophysiological activities, aiming to elucidate the potential neuroelectrophysiological mechanisms underlying the iTBS-induced improvement of social anxiety symptoms and to explore objective biomarkers for predicting treatment response. To strictly control confounding factors and ensure the double-blind design and participant safety, rigorous screening criteria have been established for this study. Inclusion criteria require participants to be right-handed individuals aged 16 to 70 years who meet the DSM-5 diagnostic criteria for SAD. If participants are taking psychiatric medications, their dosage must have been stable for at least 4 weeks prior to enrollment, and they must voluntarily sign an informed consent form. Exclusion criteria encompass patients with severe neurological or somatic diseases (e.g., epilepsy, central nervous system tumors, or stroke), those meeting DSM-5 criteria for other major psychiatric disorders, individuals with metallic implants or TMS contraindications, those with a previous history of TMS treatment, and those who have taken adequate doses of benzodiazepines for more than 2 weeks currently or within the past 4 weeks. The study spans approximately 9 weeks, comprising 1 week of intensive intervention and 8 weeks of follow-up. Upon enrollment, participants will first complete the collection of demographic data and baseline clinical scales, followed by a 30-minute pre-test of resting-state and task-state EEG. Subsequently, participants will be randomly assigned in a double-blind manner to the Left PFC-iTBS group, Right PFC-iTBS group, or Sham group. They will receive a 1-week intensive intervention at an intensity of 120% of the resting motor threshold (RMT), administered 4 times a day for 5 consecutive days, totaling 20 sessions. Immediately following the 1-week intervention, the research team will conduct an EEG post-test and synchronously collect scale data and record any adverse events. Thereafter, participants are required to attend regular follow-up visits at weeks 2, 4, 6, and 8 post-intervention to determine the long-term maintenance effects of the treatment. Regarding outcome assessments, this study establishes a multidimensional evaluation system integrating clinical scales with objective electrophysiological measures. The primary clinical outcome measure is the Liebowitz Social Anxiety Scale (LSAS), which will be assessed at baseline, immediately post-intervention, and at all follow-up time points. Secondary clinical indicators include the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and a cognitive function assessment scale. Furthermore, the study will extract resting-state and task-state EEG features and conduct brain functional network analysis as key neurophysiological outcome measures to comprehensively evaluate changes in cerebral physiological states.

Conditions

• Social Anxiety Disorder (SAD)

Interventions

Type	Name	Description
DEVICE	Active Intermittent Theta-Burst Stimulation (iTBS)	Active iTBS is delivered using a real "figure-8" coil targeting the prefrontal cortex. Stimulation is delivered at 120% of the resting motor threshold (RMT). The protocol consists of 3 sets of 50 Hz pulses repeated at 5 Hz (2s on, 8s off), totaling 1,800 pulses per session. The intensive treatment schedule includes 4 sessions per day for 5 consecutive days (1 week), totaling 20 sessions.
DEVICE	Sham Intermittent Theta-Burst Stimulation (iTBS)	Sham iTBS is delivered using a visually identical sham "figure-8" coil. It produces similar acoustic clicks and scalp somatic sensations to mimic the active treatment, ensuring participant blinding. However, it uses same-direction currents causing opposing central currents, resulting in near-zero focal magnetic induction without therapeutic effect. The session schedule and apparent parameters strictly match the active group (4 sessions/day for 5 days).

Timeline

• Start date: 2025-12-09
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2026-03-12
• Last updated: 2026-03-12

Locations

1 site across 1 country: China