Clinical trial NCT06769243: Cognitive Flexibility and Response to TMS Therapy
Official title: Cognitive Flexibility and Response to TMS Therapy in Obsessive-Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Cognitive Flexiblity
Keywords: TMS
Cognitive Felxibility
Obsessive
Compulsive
Treatment Response
Lead sponsor: Gulhane Training and Research Hospital
Sponsor class: OTHER_GOV
First posted: 2025-01-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The treatment-resistant OCD group will be evaluated both before and after TMS treatment. Cognitive flexibility levels of patients will be assessed only prior to the TMS procedure. A control group consisting of healthy participants will be evaluated solely from a neuropsychological and clinical perspective, without undergoing TMS treatment.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The Effect of Cognitive Flexibility on TMS Treatment Response
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Cognitive Flexibility Features in TMS Responders vs. Non-Responders
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Improvement of the Obsessive-Compulsive Scale: Y-BOCS
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Changes in PHQ-9 Scores Among Patients with Obsessive-Compulsive Disorder
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Neuropsychological Test Changes in Obsessive-Compulsive Disorder:WCST
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Neuropsychological Test Changes in Obsessive-Compulsive Disorder: TMT A/B
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Memory Performance in Obsessive-Compulsive Disorder: Verbal Fluency Test (VF)"
timeFrame: From enrollment to the end of treatment at 4 weeks
Secondary outcomes:
measure: Analyzing the Relationship Between Cognitive Flexibility and Symptom Severity
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Side Effects Assessment
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Tracking Reduction in Symptom Severity: Yale-Brown Obsessive-Compulsive Scale
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Tracking Reduction in Symptom Severity: Patient Health Questionnaire-9
timeFrame: From enrollment to the end of the treatment at 4 weeks.
measure: Drug Side Effect: Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: From enrollment to the end of treatment at 4 weeks
measure: Drug Side Effect: Visual Analog Scale (VAS)
timeFrame: From enrollment to the end of the treatment at 4 weeks.
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Gulhane Training and Research Hospital
Study officials:
affiliation: Gulhane Trainin and Research Hospital
name: BEYAZIT GARIP, Medical Doctor
role: PRINCIPAL_INVESTIGATOR
References: