Cognitive Flexibility and Response to TMS Therapy

NCT ID: NCT06769243

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-15
• Study Completion Date: 2024-03-15

Brief Summary

Transcranial Magnetic Stimulation (TMS) therapy is an approved and effective treatment option for treatment-resistant obsessive-compulsive disorder. The present study aims to investigate the relationship between cognitive flexibility and TMS treatment. The main question it aims to answer is:

Does cognitive flexibility predict the TMS treatment response rate? Patients will undergo neuropsychological tests to evaluate cognitive flexibility before the TMS application. A clinical scale to assess the severity of obsessive-compulsive symptoms will be administered using psychometric scales both before and after the TMS procedure.

TMS treatment will be applied five days a week for four weeks.

Detailed Description

This prospective cohort study aims to investigate the relationship between transcranial magnetic stimulation (TMS) and cognitive flexibility in patients with treatment-resistant obsessive-compulsive disorder (OCD). Treatment-resistant OCD represents a subset of OCD in which patients do not adequately respond to conventional treatments such as cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). Emerging evidence suggests that TMS, a noninvasive brain stimulation technique, can effectively alleviate symptoms in treatment-resistant OCD. However, its relationship with cognitive flexibility remains poorly understood.

This study seeks to fill this knowledge gap by assessing cognitive flexibility before TMS treatment to identify patients cognitively suitable for this intervention and understand how they respond to TMS. Another important factor to be investigated is whether there are differences between TMS responders and non-responders.

The study will enroll 30 patients diagnosed with treatment-resistant obsessive-compulsive disorder (OCD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Participants will undergo a TMS treatment treatment using the MagVenture™ X100™ device. The treatment protocol will include 20 sessions over four weeks, delivering a total of 24.000 pulses.

The stimulation will target the supplementary motor area (SMA), a region associated with OCD symptom regulation, with parameters optimized to achieve therapeutic effects while minimizing adverse side effects. Motor threshold measurements will be conducted prior to the initiation of treatment and adjusted weekly to ensure consistent treatment intensity.

A control group of 60 healthy participants will undergo a single neuropsychological evaluation for baseline comparison but will not receive TMS treatment or follow-up.

Comprehensive neuropsychological and clinical psychometric assessments will be conducted for all patients prior to the TMS treatment. After completing the 20 sessions of TMS treatment, patients will undergo clinical psychometric evaluations again.

The neuropsychological assessments will include the Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Verbal Fluency (VF) test. Psychiatric assessments will utilize the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Patient Health Questionnaire (PHQ-9), and Clinical Global Impression-Improvement (CGI-I) scale to evaluate changes in the severity of OCD symptoms.

The primary objective is to determine whether cognitive flexibility in OCD patients plays a role in predicting the response to TMS treatment. Secondary objectives include identifying any differences in cognitive flexibility test results between TMS responders and non-responders.

The primary outcomes will focus on whether cognitive flexibility-defined as the ability to adapt and cope with stress-affects the outcome of TMS treatment. This is particularly important for identifying patients who are likely to benefit from this time-intensive and prolonged treatment. Knowing in advance which patients are unlikely to respond to TMS treatment could help guide them toward alternative therapies, benefiting both patients and physicians.

Additionally, although TMS is highly effective for OCD treatment, literature suggests that up to half of patients do not respond. Understanding whether these non-responders are cognitively inflexible could help identify specific cognitive subtypes of OCD patients. This knowledge would be invaluable for tailoring treatments and improving outcomes for this challenging subset of patients.

Conditions

Obsessive-Compulsive Disorder; Cognitive Flexiblity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cognitive Flexibility

The TMS protocol was conducted using the MagVenture X100 device. Prior to treatment, a pre-evaluation was performed based on the pre-treatment risk assessment form for patients included in the study. Motor threshold measurement was carried out before the TMS application and repeated weekly. The treatment intensity was set at 100% of the measured motor threshold. As part of the OCD protocol, patients were subjected to 1 Hz rTMS pulses for 300 seconds, with a 60-second intertrain interval, totaling 1200 pulses per session. Each patient received 20 treatment sessions, resulting in a total of 24,000 pulses. The bilateral supplementary motor area (SMA) was targeted. To locate the SMA, after identifying the cranial apex, 15% of the total distance from the front was calculated.

Group Type: EXPERIMENTAL

TMS

Intervention Type: DEVICE

Transcranial Magnetic Stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain. It is primarily used to treat OCD, particularly in patients who have not responded well to traditional treatments such as medications or psychotherapy. The most common target is the supplementary motor area (SMA), which has an indirect connection with the Cortico-Striato-Thalamo-Cortical (CSTC) pathway, known to be hyperactive in OCD.

Another option to target the CSTC pathway is deep TMS, although it is not available in most advanced centers. The magnetic pulses from TMS stimulate or inhibit brain activity in the targeted area, which is believed to help reset or correct neural activity patterns associated with OCD and other psychiatric disorders.

TMS represents an alternative treatment for those struggling with OCD, offering a non-invasive approach with relatively few side effects and significant potential benefits.

Interventions

TMS

Transcranial Magnetic Stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain. It is primarily used to treat OCD, particularly in patients who have not responded well to traditional treatments such as medications or psychotherapy. The most common target is the supplementary motor area (SMA), which has an indirect connection with the Cortico-Striato-Thalamo-Cortical (CSTC) pathway, known to be hyperactive in OCD.

Another option to target the CSTC pathway is deep TMS, although it is not available in most advanced centers. The magnetic pulses from TMS stimulate or inhibit brain activity in the targeted area, which is believed to help reset or correct neural activity patterns associated with OCD and other psychiatric disorders.

TMS represents an alternative treatment for those struggling with OCD, offering a non-invasive approach with relatively few side effects and significant potential benefits.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• According to the DSM-5 TR, those diagnosed with Obsessive-Compulsive Disorder (OCD),
• Failure to respond to at least two different antidepressants and anti-obsessive agents at effective doses and durations,
• The condition cannot be better explained by a metabolic or organic disorder,
• No contraindications to treatment were identified based on the risk assessment scale applied before TMS.

Exclusion Criteria

• Detection of a contraindication for treatment based on the pre-TMS risk assessment form,
• Detection of an epileptic focus in the pre-TMS electroencephalography findings,
• Diagnosis of a psychotic disorder or bipolar mood disorder,
• Active suicidal thoughts and high risk for suicide,
• The participant to be included in the study has a history of alcohol, substance, or stimulant abuse or addiction (excluding cases where they have not used these substances in the last 12 months or have no history of alcohol misuse), based on a semi-structured clinical interview.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gulhane Training and Research Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Beyazit Garip

Director of Gulhane Brain Stimulation Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

BEYAZIT GARIP, Medical Doctor

Role: PRINCIPAL_INVESTIGATOR

Gulhane Trainin and Research Hospital

Locations

Gulhane Training and Research Hospital

Ankara, Ankara, Turkey (Türkiye)

Countries

Turkey (Türkiye)

Other Identifiers

2023-19

Identifier Type: -

Identifier Source: org_study_id