Cognitive Flexibility and Response to TMS Therapy

NCT06769243 | Completed

• 1 other identifier: 2023-19
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive-Compulsive Disorder; Cognitive Flexiblity

Keywords

TMS; Cognitive Felxibility; Obsessive; Compulsive; Treatment Response

Outcome Measures

Primary Outcomes (7)

• The Effect of Cognitive Flexibility on TMS Treatment Response

  The changes in psychometric scales before and after TMS treatment will determine whether a patient is a TMS responder. Cognitive flexibility, measured at the beginning of treatment, may influence the changes in these psychometric scales. This study will examine the relationship between TMS response rate and cognitive flexibility in OCD patients.

  From enrollment to the end of treatment at 4 weeks

• Cognitive Flexibility Features in TMS Responders vs. Non-Responders

  Cognitive flexibility features in TMS responders will be compared with non-responders and healthy controls. Specific features in responders vs. non-responders will be evaluated in detail. Cognitive flexibility may be identified as a distinguishing factor in OCD subtypes within the non-responder group. This could be useful for navigating treatment options at the beginning of the TMS procedure.

  From enrollment to the end of treatment at 4 weeks

• Improvement of the Obsessive-Compulsive Scale: Y-BOCS

  A reduction of more than 30% in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score will be used to evaluate treatment response. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is commonly used to assess the severity of obsessive-compulsive disorder (OCD).The Y-BOCS consists of 10 items, each rated on a scale from 0 (no symptoms) to 4 (extreme symptoms). These items are divided into obsessions (5 items) and compulsions (5 items), allowing for a subscore for each domain (maximum of 20 each). Minimum Score: 0 (indicating no symptoms). Maximum Score: 40 (indicating extreme severity of symptoms)

  From enrollment to the end of treatment at 4 weeks

• Changes in PHQ-9 Scores Among Patients with Obsessive-Compulsive Disorder

  The Patient Health Questionnaire-9 (PHQ-9) is a self-administered tool used to screen, diagnose, monitor, and measure the severity of depression. A clinical response is typically defined by a measurable reduction in symptom severity, in depression, a clinical response is defined as a 50% or greater reduction in scores on PHQ-9. The PHQ-9 (Patient Health Questionnaire-9) has the following scoring range: Minimum Score: 0 (indicating no depressive symptoms). Maximum Score: 27 (indicating severe depressive symptoms).

  From enrollment to the end of treatment at 4 weeks

• Neuropsychological Test Changes in Obsessive-Compulsive Disorder:WCST

  The Wisconsin Card Sorting Test (WCST) is a neuropsychological test designed to evaluate executive functions, including cognitive flexibility, problem-solving, and the ability to adapt to changing rules. It is commonly used in research and clinical settings to assess individuals with neurological or psychiatric conditions Measures and Scoring: Number of Categories Completed: Indicates how many correct sorting rules the participant identified. Perseverative Errors: Reflects the tendency to persist with an incorrect rule despite feedback. Non-perseverative Errors: Errors that are not related to the previously learned rule. Failure to Maintain Set: Reflects the inability to consistently apply a correct sorting rule. Trials to Complete the First Category: Measures the efficiency in initially identifying a rule.

  From enrollment to the end of treatment at 4 weeks

• Neuropsychological Test Changes in Obsessive-Compulsive Disorder: TMT A/B

  The Trail Making Test (TMT) is a neuropsychological assessment tool used to measure cognitive flexibility, processing speed, and executive functioning. TMT-A: Normal Performance: Typically, scores are within 30-60 seconds for healthy adults. Slower Time: Suggests processing speed or attention difficulties, which may be seen in conditions such as ADHD, depression, or neurological impairments. TMT-B: Normal Performance: Usually takes 60-150 seconds for healthy adults. Slower Time: A significant delay in TMT-B (compared to TMT-A) can suggest difficulty with task-switching, cognitive flexibility, or executive function, often seen in frontal lobe dysfunction, dementia, Parkinson's disease, or other cognitive impairments.

  From enrollment to the end of treatment at 4 weeks

• Memory Performance in Obsessive-Compulsive Disorder: Verbal Fluency Test (VF)"

  Verbal Fluency Test (VFT), is a neuropsychological test that measures a person's ability to generate words within a specific category (semantic fluency) or starting with a specific letter (phonemic fluency) in a set amount of time. It is used to assess executive functions, language, and cognitive flexibility. Semantic Fluency (Category Fluency): The participant is asked to name as many items as possible within a given category, such as animals or fruits, in 60 seconds. Phonemic Fluency (Letter Fluency): The participant is asked to generate as many words as possible that begin with a given letter (e.g., "K", "A", or "S") in 60 seconds. Scoring: The score is based on the number of words the participant can generate within the time limit.

  From enrollment to the end of treatment at 4 weeks

Secondary Outcomes (6)

• Analyzing the Relationship Between Cognitive Flexibility and Symptom Severity

  From enrollment to the end of treatment at 4 weeks

• Side Effects Assessment

  From enrollment to the end of treatment at 4 weeks

• Tracking Reduction in Symptom Severity: Yale-Brown Obsessive-Compulsive Scale

  From enrollment to the end of treatment at 4 weeks

• Tracking Reduction in Symptom Severity: Patient Health Questionnaire-9

  From enrollment to the end of the treatment at 4 weeks.

• Drug Side Effect: Common Terminology Criteria for Adverse Events (CTCAE)

  From enrollment to the end of treatment at 4 weeks

Study Arms (1)

Cognitive Flexibility

EXPERIMENTAL

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.

Device: TMS

Interventions

TMS 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.

Cognitive Flexibility

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gulhane Training and Research Hospital: lead

Study Sites (1)

Gulhane Training and Research Hospital

Ankara, Ankara, 06000, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Study Officials

• BEYAZIT GARIP, Medical Doctor

  Gulhane Trainin and Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Gulhane Brain Stimulation Center

Model Details: 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.

Study Record Dates

• First Submitted: December 29, 2024
• First Posted: January 10, 2025
• Study Start: April 15, 2023
• Primary Completion: February 20, 2024
• Study Completion: March 15, 2024
• Last Updated: January 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: The data will be made available immediately after the publication, and will remain available for at least 5 years.
• Access Criteria: Anyone who wishes to access the data

Locations

TU (1)