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Effect of Deep TMS on the Permeability of the BBB in Patients With Glioblastoma Multiforme: a Pilot Study

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ClinicalTrials.gov Identifier: NCT02474966
Recruitment Status : Completed
First Posted : June 18, 2015
Last Update Posted : June 18, 2015
Sponsor:
Information provided by (Responsible Party):
Maurizio Inghilleri, University of Roma La Sapienza

Brief 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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme of Brain Device: Deep Transcranial Magnetic Stimulation (dTMS) Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of Deep Transcranial Magnetic Stimulation on the Permeability of the Blood-brain Barrier in Patients With Glioblastoma Multiforme: a Pilot Study
Study Start Date : November 2014
Actual Primary Completion Date : April 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Real-Sham dTMS
This arm will be treated before with real deep Transcranial Magnetic Stimulation (dTMS) (the first day) and after with sham dTMS (the second day)
Device: Deep Transcranial Magnetic Stimulation (dTMS)
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.

Experimental: Sham-Real dTMS
This arm will be treated before with sham deep Transcranial Magnetic Stimulation (dTMS) (the first day) and after with real dTMS (the second day)
Device: Deep Transcranial Magnetic Stimulation (dTMS)
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.




Primary Outcome Measures :
  1. Change in blood-brain barrier permeability [ Time Frame: Six months ]
    The efficacy of the deep Transcranial Magnetic Stimulation (dTMS) in modulating blood-brain barrier permeability in patients with glioblastoma multiforme through the measurement of the average value of the slope-value distribution function (CDF) evidenced with dynamic contrast-enhanced magnetic resonance imaging


Secondary Outcome Measures :
  1. Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Six months ]
    To evaluate the safety of the deep Transcranial Magnetic Stimulation (dTMS) applied in patients with glioblastoma multiforme



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Histological diagnosis of glioblastoma multiforme (WHO grade IV)
  • Craniotomy with resection of the tumor at least one year prior to the study
  • Treatment with steroids or chemotherapy stable for at least four weeks prior to study enrollment

Exclusion Criteria:

  • History of epilepsy
  • Presence of cardiac pacemaker
  • Presence of neurostimulators
  • Presence of surgical clips or medical pumps
  • Allergy to contrast medium for Magnetic Resonance Imaging
  • History of head injuries
  • Alcoholism or drugs abuse
  • State of pregnant or breastfeeding
  • Severe psychiatric disorders

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02474966


Sponsors and Collaborators
University of Roma La Sapienza
Investigators
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Principal Investigator: Maurizio Inghilleri, Professor University "Sapienza" of Rome

Publications of Results:

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Responsible Party: Maurizio Inghilleri, Principal Investigator, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT02474966     History of Changes
Other Study ID Numbers: 3403/23.10.14
First Posted: June 18, 2015    Key Record Dates
Last Update Posted: June 18, 2015
Last Verified: June 2015

Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue