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

NCT ID: NCT02474966

Last Updated: 2015-06-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-30

Study Completion Date

2015-05-31

Brief Summary

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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

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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.

Conditions

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Glioblastoma Multiforme of Brain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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)

Group Type EXPERIMENTAL

Deep Transcranial Magnetic Stimulation (dTMS)

Intervention Type DEVICE

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.

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)

Group Type EXPERIMENTAL

Deep Transcranial Magnetic Stimulation (dTMS)

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Roma La Sapienza

OTHER

Sponsor Role lead

Responsible Party

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Maurizio Inghilleri

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Maurizio Inghilleri, Professor

Role: PRINCIPAL_INVESTIGATOR

University "Sapienza" of Rome

References

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Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

Reference Type RESULT
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Roth Y, Zangen A, Hallett M. A coil design for transcranial magnetic stimulation of deep brain regions. J Clin Neurophysiol. 2002 Aug;19(4):361-70. doi: 10.1097/00004691-200208000-00008.

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Wassermann EM, Zimmermann T. Transcranial magnetic brain stimulation: therapeutic promises and scientific gaps. Pharmacol Ther. 2012 Jan;133(1):98-107. doi: 10.1016/j.pharmthera.2011.09.003. Epub 2011 Sep 7.

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Sharp CD, Hines I, Houghton J, Warren A, Jackson TH 4th, Jawahar A, Nanda A, Elrod JW, Long A, Chi A, Minagar A, Alexander JS. Glutamate causes a loss in human cerebral endothelial barrier integrity through activation of NMDA receptor. Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2592-8. doi: 10.1152/ajpheart.00520.2003. Epub 2003 Jul 31.

Reference Type RESULT
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Mottaghy FM, Gangitano M, Horkan C, Chen Y, Pascual-Leone A, Schlaug G. Repetitive TMS temporarily alters brain diffusion. Neurology. 2003 May 13;60(9):1539-41. doi: 10.1212/01.wnl.0000058903.15205.46.

Reference Type RESULT
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Chassidim Y, Veksler R, Lublinsky S, Pell GS, Friedman A, Shelef I. Quantitative imaging assessment of blood-brain barrier permeability in humans. Fluids Barriers CNS. 2013 Feb 7;10(1):9. doi: 10.1186/2045-8118-10-9.

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Reference Type RESULT
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Other Identifiers

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3403/23.10.14

Identifier Type: -

Identifier Source: org_study_id

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