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
Condition: OCD
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      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
    

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.
    

Intervention name(s): continuous theta burst stimulation - cTBS
Intervention type(s): Device
Intervention description(s): Continuous theta burst stimulation (cTBS) is a quicker and potentially more effective technique to reduce cortical hyperactivity than repetitive transcranial magnetic stimulation (rTMS). The study involves a cycle of 35 cTBS stimulations 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMS; OCD; cTBS; BDNF; Neuroplasticity