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

June 17, 2015 updated by: Maurizio Inghilleri, University of Roma La Sapienza

Effects of Deep Transcranial Magnetic Stimulation on the Permeability of the Blood-brain Barrier in Patients With Glioblastoma Multiforme: a Pilot Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Six months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Roma La Sapienza

Investigators

  • Principal Investigator: Maurizio Inghilleri, Professor, University "Sapienza" of Rome

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

June 11, 2015

First Submitted That Met QC Criteria

June 17, 2015

First Posted (Estimate)

June 18, 2015

Study Record Updates

Last Update Posted (Estimate)

June 18, 2015

Last Update Submitted That Met QC Criteria

June 17, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3403/23.10.14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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