pBFS Guided rTMS Therapy for Treatment-resistant Obsessive-Compulsive Disorder

Personalized Brain Functional Sectors (pBFS) Guided rTMS Therapy for Treatment-resistant Obsessive-Compulsive Disorder: A Randomized, Double-Blind, Sham-controlled Trial

The investigators aim to evaluate the safety and efficacy of pBFS-guided rTMS therapy targeting DLPFC for patients with treatment-resistant Obsessive-Compulsive Disorder.

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder; OCD
• Intervention / Treatment: Device: sham rTMS treatment; Device: active rTMS treatment

Detailed Description

In 2018, rTMS received approval from the U.S. Food and Drug Administration (FDA) for the treatment of OCD. Based on randomized clinical trials, researchers have observed significant variations in the intervention effects when targeting the dorsolateral prefrontal cortex (DLPFC), which is a large region with different subregions and functional connections to other areas across multiple functional networks. Precise targeting of neural circuitry related to OCD symptoms is crucial for effective intervention. The ventrolateral prefrontal cortex and insula are key components of the OCD functional circuitry within the ventral attention/salience network. However, stimulating these brain regions with TMS is challenging, and patients often have a low tolerance. Previous studies have found that effective targets for various interventions used in psychiatric disorders are located within the same functional circuitry. Therefore, in this study, The investigator employed the pBFS technique to precisely locate the DLPFC subregions within the ventral attention/salience network. The investigator hypothesizes that rTMS intervention targeting the DLPFC guided by pBFS will significantly alleviate clinical symptoms in treatment-resistant OCD patients.

After being informed about the study and potential risks. All patients giving written informed consent will undergo a screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a double-blind manner in a 2:1 ratio to the active rTMS group, or sham-control group. Then all participants will undergo a 15-day （3 weeks， treatment on weekdays） rTMS modulation. After treatment, 15-, 30-, 60-, and 90-day follow-up visits will occur. Participants will keep a stable treatment regimen during the intervention and the first-month follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Meiling Li, Ph.D.; Phone Number: 010-80726688; Email: meilingli@cpl.ac.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Peking University Six Hospital
      • Contact: Jinmin Liao

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Hospitalized/outpatient patients aged 18-65 years (inclusive), male or female.
• Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) for obsessive-compulsive disorder, and currently experiencing a first or recurrence episode.
• Total Y-BOCS score ≥20 and total HAMD score <17 before randomization.
• Before randomization, patients must have received a minimum of 2 months of maintenance treatment with SSRI medication prior to randomization, or have undergone maintenance CBT treatment with inadequate response to SSRI medication (less than 50% symptom improvement), or have previously shown inadequate response (less than 50% symptom improvement) to at least one trial of SSRI medication or cognitive-behavioral therapy. Patients currently taking medication should have been on a stable dose for 8 weeks.
• Voluntarily participate in the trial and sign informed consent. Able to comply with the planned visit, examination and treatment plan, and other study procedures.

Exclusion Criteria:

• Meet DSM-5 diagnostic criteria for other mental disorders (such as schizophrenia, schizoaffective disorder, post-traumatic stress disorder, bipolar disorder, and secondary depression, etc.);
• Patients with a cardiac pacemaker, cochlear implant, or other metal foreign body and any electronic equipment implanted in the body, patients with claustrophobia and other contraindications to magnetic resonance scanning, and patients with contraindications to rTMS treatment;
• History of epilepsy (presence of at least 2 uninduced seizures more than 24 hours apart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months); Or currently received medications or other treatments that will lower the seizure threshold;
• History of ECT, rTMS, light therapy within 3 months;
• Patients with organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain tumor, etc.) and a history of severe brain trauma as judged by the researcher;
• Patients with serious or unstable diseases of the cardiovascular, liver, kidney, blood, endocrine, neurological system, and other systems or organs.
• Female of childbearing potential who plans to become pregnant during the trial. Female that is pregnant or breastfeeding.
• Substance abuse or dependence (including alcohol, drugs, and other psychoactive substances) in the past 6 months.
• First-degree relatives have bipolar affective disorder and schizophrenia.
• There is a significant risk of suicide (MADRS item 3 ≥ 3).
• Difficulty or inability to engage in normal communication, understand or follow instructions, and cooperate with treatment and evaluators.
• Patients in any clinical trials of other drugs or physical therapy ( DBS, ECT, rTMS) within 1 month before the screening
• Investigators think that was inappropriate to participate.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active rTMS treatment; 5 sessions of active rTMS would be delivered to the left DMPFC daily, with a session of 1800 pulse and inter-session interval of 20 min.	Device: active rTMS treatment; Participants will receive 5 sessions per day of 1800 pulses per session, lasting for 15 days. Individualized targets will be generated using the pBFS method.
Sham Comparator: sham control; 5 sessions of sham rTMS would be delivered to the left DMPFC daily, with a session of 1800 pulse and inter-session interval of 20 min.	Device: sham rTMS treatment; The parameters in the sham arms are the same as the active stimulation groups. Stimulation was delivered by the same device as the active group fitted with a sham coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	The Y-BOCS is a validated instrument stratifying the severity of obsessive episodes. This validated questionnaire was used to assess the response rate and remission rate of obsessive episodes. The response is defined as a symptom improvement of ≥35% on Y-BOCS;	Baseline, Day 15(immediate post-treatment), 15- and 30-day post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
remission rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Remission was defined as a score <8.	Baseline, Day 15(immediate post-treatment), 15- and 30-day post-treatment
Partial response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Partial response is defined as a symptom 35% ≥ improvement ≥25% on Y-BOCS	Baseline, Day 15(immediate post-treatment), 15- and 30-day post-treatment
cognitive change in stroop	The Stroop test can be used to measure a person's selective attention capacity and skills, processing speed, and alongside other tests to evaluate overall executive processing abilities	Baseline, Day 15(immediate post-treatment)
cognitive change in Hopkins verbal learning test(immediate recall)	The Hopkins Verbal Learning Test (HVLT-R) is one such assessment that consists of memorization of a list of words to test the ability to recall immediately after memorization	Baseline, Day 15(immediate post-treatment)
cognitive change in Trail-Making Test	The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning	Baseline, Day 15(immediate post-treatment)

Collaborators and Investigators

• Sponsor: Changping Laboratory
• Investigators: Study Chair: Hesheng Liu, Ph.D., Changping Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2023
• Primary Completion (Estimated): July 20, 2024
• Study Completion (Estimated): October 20, 2024

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: OCD; Obsessive-Compulsive Disorder; Treatment-resistant OCD
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
• Other Study ID Numbers: CPLOCDDLPFC

Drug and device information, study documents

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