Explore Neural Mechanism of OCD by Intervention of Repetitive Transcranial Magnetic Stimulation With Symptom Provocation

The purpose of this study is to investigate the differences in therapeutic efficacy of different deep TMS treatment coils and different brain stimulation targets on obsessive-compulsive symptoms, and to explore the neural mechanisms of obsessive-compulsive disorder using functional neuroimaging analysis.

1. Inclusion Criteria:

   Adults aged 18-65 years. Patients diagnosed with obsessive-compulsive disorder according to DSM-5 criteria.

2. Study Design: Double-blind, randomized assignment.

3. Number of Participants:

   Sham group: 32 participants Active H7 group: 32 participants Active H1 group: 32 participants Total: 96 participants

4. Study Procedures:

   - Participant Screening and Baseline Assessment (Week 0) Determine eligibility for enrollment, including diagnostic confirmation, symptom assessment, screening for contraindications, and whether the participant has previously experienced adverse effects following TMS treatment. Participants with high suicide risk within the past year will be excluded.

   Develop a personalized symptom provocation procedure for obsessive-compulsive symptoms (Carmi et al., 2018).

   Complete baseline symptom severity assessments and brain positron emission tomography/magnetic resonance imaging (PET/MRI). Participants with structural brain abnormalities will be excluded.

   Participants will be randomly assigned (1:1:1) into three groups, with a planned total enrollment of 96 participants.

   Participants currently taking medication may continue their existing regimen, but no medication changes will be allowed during the study period.

   - Treatment Phase (Week 1 to Week 6; duration: 6 weeks) Before each TMS session, participants will remove their shoes and socks, rest both hands flat on their thighs, keep their eyes looking straight ahead, and undergo measurement of resting motor threshold (RMT).

   Approximately 3-5 minutes before each TMS session, trained personnel with ERP experience will assist participants in symptom provocation and record the participant's subjective level of distress.

   The deep TMS treatment schedule consists of five sessions per week, one session per day, for six consecutive weeks. Adverse effects will be assessed and monitored at each session.

   After completing the first treatment session, participants will be asked to guess which group they were assigned to, in order to evaluate the effect of treatment expectations on outcomes.

   Symptom severity interviews will be conducted every two weeks.

   - Post-treatment Assessment and Follow-up (Week 7 and after; duration: 2 weeks, then 6 months later) Within one week after completion of the deep TMS treatment course (within Week 7), participants will undergo follow-up brain PET/MRI.

   At the end of Week 8 (two weeks after treatment completion), symptom severity will be reassessed. Subsequent treatment plans will be discussed with participants, and outpatient follow-up will be arranged within six months.

   Subsequent treatment options may include cognitive behavioral therapy, pharmacotherapy, and figure-8 rTMS.

5. Statistical Analysis

   • Expected Outcomes:

The H7 coil may improve obsessive-compulsive symptoms. Both the H7 and H1 coils may improve mood symptoms.

- Descriptive and Inferential Statistics: Analysis of covariance (ANCOVA) will be used to compare differences among the three groups in MADRS, Y-BOCS, HAM-A, HDRS, and CGI-S scores.

The percentage of responders (% responders) will be calculated and compared among groups.

Repeated-measures ANOVA will be used to examine within-group and between-group differences in symptom improvement before and after deep TMS treatment.

Pearson correlation analysis will be used to assess the association between symptom improvement and changes observed in PET/MRI neuroimaging measures.

- PET/MRI Neuroimaging Analysis: Functional MRI analyses will include ROI-to-ROI functional connectivity and seed-based functional connectivity analyses.

Changes in PET glucose uptake within specific regions of interest (ROIs) will also be examined to evaluate alterations in neural networks and brain function before and after deep TMS treatment.

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder (OCD)
• Intervention / Treatment: Device: Sham deep TMS (control stimulation) & H7 deep TMS (active treatment) & H1 deep TMS (active treatment)

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cheng-Ta Li; Phone Number: 886-2-55704055; Email: ctli0420@gmail.com
• Study Contact Backup: Name: Chia-Min Huang; Email: psygrace1@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Cheng-Ta Li; Phone Number: 886-2-55704055; Email: ctli0420@gmail.com
    • Contact: Chia-Min Huang; Email: psygrace1@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18-65 years.
• Diagnosis of obsessive-compulsive disorder according to DSM-5 criteria. Treatment resistance (i.e., inadequate response to pharmacological or non-pharmacological treatments) is not required.
• Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score ≥ 14, indicating at least mild to moderate symptom severity.

Exclusion Criteria:

• Diagnosis of schizophrenia, organic psychotic disorder, bipolar disorder, alcohol use disorder, or substance use disorder.
• High suicide risk within the past year.
• Presence of significant medical or surgical conditions in an active phase.
• History of, or planned, neurosurgical procedures, or presence of metallic implants in the brain or body (e.g., neurostimulators or cardiac pacemakers).
• Structural brain abnormalities (e.g., brain tumor or arteriovenous malformation) or neurological disorders (e.g., meningitis, encephalitis, stroke, or epilepsy).
• Pregnant women.
• Inability to tolerate PET/MRI examination due to claustrophobia or severe anxiety in confined spaces.
• Any other conditions that may impair study compliance, including inability to cooperate, failure to provide informed consent, or other investigator-determined ineligibility after screening.
• Use of medications that may increase seizure risk or suicide risk (e.g., certain antidepressants or antipsychotics).
• Known allergy to 18F-FDG.
• History of adverse reaction to TMS or allergy to the positioning cap.
• Presence of metallic objects within approximately 30 cm of the cranial region (within the stimulation coil area).
• Prior or current treatment with electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active H7 coil stimulation	Device: Sham deep TMS (control stimulation) & H7 deep TMS (active treatment) & H1 deep TMS (active treatment); Sham dTMS Participants will receive sham deep TMS using a sham coil. H7 dTMS Participants will receive active deep TMS using the H7 coil. H1 dTMS Participants will receive active deep TMS using the H1 coil.
Sham Comparator: Sham stimulation group	Device: Sham deep TMS (control stimulation) & H7 deep TMS (active treatment) & H1 deep TMS (active treatment); Sham dTMS Participants will receive sham deep TMS using a sham coil. H7 dTMS Participants will receive active deep TMS using the H7 coil. H1 dTMS Participants will receive active deep TMS using the H1 coil.
Experimental: Active H1 coil group	Device: Sham deep TMS (control stimulation) & H7 deep TMS (active treatment) & H1 deep TMS (active treatment); Sham dTMS Participants will receive sham deep TMS using a sham coil. H7 dTMS Participants will receive active deep TMS using the H7 coil. H1 dTMS Participants will receive active deep TMS using the H1 coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the percentage changes in Y-BOCS scores after treatments	Two time-spans are assessed: (a) from baseline (Week 0, W0) to posttreatment (Week 6, W6), and (b) from baseline (W0) to the 2-week follow-up (Week 8, W8). The percentage changes in Y-BOCS scores will be calculated as follows: % of YBOCS6-0 = (W6 - W0) / W0; % of YBOCS8-0 = (W8 - W0) / W0 A full treatment response, defined as a ≥30% reduction in Y-BOCS score from baseline, will be evaluated at both the 6-week and 8-week time points.	the 6-week and 8-week

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan

Publications and helpful links

General Publications

• Carmi L, Alyagon U, Barnea-Ygael N, Zohar J, Dar R, Zangen A. Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients. Brain Stimul. 2018 Jan-Feb;11(1):158-165. doi: 10.1016/j.brs.2017.09.004. Epub 2017 Sep 6.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 8, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Obsessive-Compulsive Disorder
• Other Study ID Numbers: 2024-06-004C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No