Clinical trial NCT05964049: pBFS Guided rTMS Therapy for Treatment-resistant Obsessive-Compulsive Disorder
Official title: Personalized Brain Functional Sectors (pBFS) Guided rTMS Therapy for Treatment-resistant Obsessive-Compulsive Disorder: A Randomized, Double-Blind, Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obsessive-Compulsive Disorder
OCD
Keywords: Obsessive-Compulsive Disorder
OCD
Treatment-resistant OCD
Lead sponsor: Changping Laboratory
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
timeFrame: Baseline, Day 15(immediate post-treatment), 15- and 30-day post-treatment
Secondary outcomes:
measure: remission rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
timeFrame: Baseline, Day 15(immediate post-treatment), 15- and 30-day post-treatment
measure: Partial response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
timeFrame: Baseline, Day 15(immediate post-treatment), 15- and 30-day post-treatment
measure: cognitive change in stroop
timeFrame: Baseline, Day 15(immediate post-treatment)
measure: cognitive change in Hopkins verbal learning test(immediate recall)
timeFrame: Baseline, Day 15(immediate post-treatment)
measure: cognitive change in Trail-Making Test
timeFrame: Baseline, Day 15(immediate post-treatment)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Six Hospital
state: Beijing
Study officials:
affiliation: Changping Laboratory
name: Hesheng Liu, Ph.D.
role: STUDY_CHAIR
References: