Does TMS Affect Neuroplasticity? The Role of Brain-derived Neurotrophic Factor and Neuronal Cell Adhesion Molecules - an Intensive Clinical Protocol Among Patients With Obsessive-compulsive Disorders

Patients expressing interest in participating will undergo psychiatric assessment to verify the diagnosis of treatment-resistant obsessive-compulsive disorder (OCD), assess symptom severity, and exclude TMS contraindications. The study involves a cycle of 35 continuous theta burst stimulations (cTBS) in the supplementary motor area (SMA) over 5 working days, with 7 stimulation sessions each day lasting 40 seconds. A 1-hour break between sessions will be observed, and each session will comprise 600 pulses at 90% of the motor threshold intensity.

Biochemical analysis of blood serum from 40 patients will be conducted at three time points in an open-label study with active TMS stimulation:

T0 - before starting stimulation T1 - after completing stimulation T2 - 1 month after completing stimulation

Inclusion criteria: Diagnosis of depression or OCD according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) criteria, Hamilton Depression Rating Scale (HAM-D) score > 16 points, or Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score > 19 points; age 18-70 years.

Exclusion criteria: Contraindications to TMS procedures, lack of informed consent, and documented persistent non-cooperation with treatment

Study Overview

• Status: Completed
• Conditions: OCD
• Intervention / Treatment: Device: continuous theta burst stimulation - cTBS

Detailed Description

Transcranial Magnetic Stimulation (TMS) is an accepted non-invasive method of neurostimulation. Evidence has demonstrated that TMS allows for the reduction of depression symptoms, and an increasing number of reports support its efficacy in reducing symptoms of obsessive-compulsive disorder (OCD). There is a limited body of clinical research available on the mechanisms of TMS action. Neuroplasticity refers to the capacity of neural tissue to form new connections for the purpose of reorganization and adaptation. Brain-Derived Neurotrophic Factor (BDNF) and Cell Adhesion Molecules (CAM) are markers of neuroplasticity. BDNF influences transmission in both excitatory and inhibitory synapses, enhancing neurotransmitter release in cholinergic and dopaminergic neurons. According to the neurotrophic hypothesis, stress may decrease BDNF levels. Serum BDNF concentrations are reduced in untreated patients with depression and normalized by antidepressant treatment. Neuronal CAMs are among the most prevalent proteins, playing a crucial role in synaptic plasticity. Various CAMs appear to interact with BDNF. In depression, both reduced BDNF levels and polysialylated (PSA) neuronal CAMs are observed. Conversely, the levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intracellular Adhesion Molecule-1 (ICAM-1) in depression are inversely correlated with BDNF.

To address this gap, the investiagators aimed to verify the hypothesis that TMS in OCD leads to symptom reduction by inducing neuroplasticity through:

Comparing changes in BDNF and CAM protein concentrations after TMS stimulation in OCD patients before and after stimulation.

Assessing the correlation between changes in BDNF and CAM concentrations and the reduction of psychopathological symptoms.

Evaluating the predictive value of initial BDNF and CAM concentrations.

Study assumptions and planned procedures:

Patients expressing interest in participating will undergo psychiatric assessment to verify the diagnosis of treatment-resistant OCD, assess symptom severity, and exclude TMS contraindications. The study involves a cycle of 35 cTBS stimulations in the supplementary motor area (SMA) over 5 working days, with 7 TMS sessions each day lasting 40 seconds. A 1-hour break between sessions will be observed, and each session will comprise 600 pulses at 90% of the motor threshold intensity.

Biochemical analysis of blood serum from 40 patients will be conducted at three time points in an open-label study with active TMS stimulation:

T0 - before starting stimulation T1 - after completing stimulation T2 - 1 month after completing stimulation

Inclusion criteria: Diagnosis of depression or OCD according to ICD-10 criteria, Hamilton Depression Rating Scale (HAM-D) score > 16 points, or Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score > 19 points; age 18-70 years.

Exclusion criteria: Contraindications to TMS procedures, lack of informed consent, and documented persistent non-cooperation with treatment.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Poland
  • Dolnośląskie
    • Wrocław, Dolnośląskie, Poland, 50-367
      • Department of Psychaitry Wroclaw Medical University
    • Wrocław, Dolnośląskie, Poland, 50-367
      • Deprtment of Psychiatry

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of depression or OCD according to ICD-10 criteria,
• Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score > 19 points;
• age 18-70 years.

Exclusion Criteria:

• Contraindications to TMS procedures,
• lack of informed consent, and documented persistent non-cooperation with treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OCD symptoms severity T1	OCD symptoms severity - Yale Brown Obsessive-Compulsive Scale (Y-BOCS) scoring from 0-40. Higher score means higher severity of symptoms	5 days
OCD symptoms severity T2	OCD symptoms severity - OCD symptoms severity - Yale Brown Obsessive-Compulsive Scale (Y-BOCS) scoring from 0-40. Higher score means higher severity of symptoms	30 days
depressive symptoms severity T1	depressive symptoms severity -Montgomery-Asberg Depression Rating Scale (MADRS) scoring from 0-60. Higher score means higher severity of depressive symptoms	5 days
depressive symptoms severity T2	depressive symptoms severity - depressive symptoms severity -Montgomery-Asberg Depression Rating Scale (MADRS) scoring from 0-60. Higher score means higher severity of depressive symptoms	30days

Collaborators and Investigators

• Sponsor: Wroclaw Medical University
• Investigators: Study Chair: Błażej Misiak, Prof, Department of Psychaitry Wroclaw Medical Univeristy, Pasteura 10 Str Wrocław Poland

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Actual): January 6, 2024
• Study Completion (Actual): January 6, 2024

Study Registration Dates

• First Submitted: January 7, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: OCD; Neuroplasticity; BDNF; TMS; cTBS
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
• Other Study ID Numbers: SUBK.C230.23.065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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