Effect of Deep TMS on the Permeability of the BBB in Patients With Glioblastoma Multiforme: a Pilot Study
Condition: Glioblastoma Multiforme of Brain
MeSH terms: Glioblastoma
Study type: Interventional
Phase: Phase 2

Summary: 
      The blood-brain barrier (BBB) is a specialized interface allowing a unique environment for
      neuro-glia networks. BBB dysfunction is common in brain disorders. The Transcranial Magnetic
      Stimulation (TMS) is a non-invasive method of stimulating cortical motor neurons with the use
      of rapidly changing electromagnetic fields generated by a coil placed over the scalp. The
      objective of this study is to evaluate the safety and effects of the deep TMS (dTMS) on
      barrier integrity in patients with malignant glial tumors. BBB permeability will be
      quantified using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Permeability
      change will be compared between two DCE-MRI scans performed immediately after "real" and
      "sham" rTMS, randomly assigned within one week of each other.
    

Detailed description: 
      The blood-brain barrier (BBB) is a specialized interface allowing a unique environment for
      neuro-glia networks. BBB dysfunction is common in brain disorders. However, the mechanisms
      underlying BBB opening are poorly understood. The investigators suggest a novel mechanism
      modulating BBB integrity and therapeutic implications in patients with glioblastoma
      multiforme. The Transcranial Magnetic Stimulation (TMS) is a noninvasive method of
      stimulating cortical motor neurons through the scalp and skull capable of inducing electrical
      currents and depolarizing neurons in focal brain areas with the use of rapidly changing
      electromagnetic fields generated by a coil placed over the scalp. The objective of this study
      is to evaluate the safety and effects of the deep TMS (dTMS) on barrier integrity in 20
      patients with malignant glial tumors (glioblastoma multiforme). BBB permeability will be
      quantified using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Permeability
      change will be compared between two DCE-MRI scans performed immediately after "real" and
      "sham" dTMS, randomly assigned within one week of each other.

      Design of study: Randomized double-blind crossover study. Patients will present on two
      consecutive days in order to receive dTMS followed by DCE-MRI. Subjects will be randomized
      into two groups: the first group will be treated before with real-dTMS (the first day) and
      after with sham-dTMS (the second day); the second group will be treated before with sham-dTMS
      (the first day) and after with real-dTMS (the second day). At the end of each session of dTMS
      the patients will undergo by MRI exams.

      Enrolled patients: twenty patients with glioblastoma multiforme treated with craniotomy and
      gross tumor resection or maximal debulking at least a year prior to the study and treated
      with standard post-operative radiotherapy and adjuvant chemotherapy.

      dTMS will be delivered at 1 Hz, on the anterior periphery of the resected tumor bed using the
      Hesed-coil (H-coil) (Brainsway Ltd., Jerusalem, Israel). Sham stimulation will be delivered
      with a sham coil placed in the same helmet able to produce similar sounds and scalp
      sensations.
    

Intervention name(s): Deep Transcranial Magnetic Stimulation (dTMS)
Intervention type(s): Device
Intervention description(s): Patients will present on two consecutive days in order to receive dTMS followed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Subjects will be randomized into two groups: the first group will be treated before with real-dTMS (the first day) and after with sham-dTMS (the second day); the second group will be treated before with sham-dTMS (the first day) and after with realTMS (the second day). At the end of each session of dTMS the patients will undergo by MRI exams.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science