Induction of Cortical Plasticity

Induction of Cortical Plasticity by Navigated Transcranial Magnetic Stimulation

The study aims to induce plastic reorganization by a therapeutic protocol to increase the rate of gross total resection (GTR) and to optimize the oncological result.

Study Overview

• Status: Recruiting
• Conditions: Adult Brain Tumor
• Intervention / Treatment: Device: Navigated repetitive transcranial magnetic stimulation

Detailed Description

Regarding the therapy of cerebral parenchyma tumors, the extent of resection (EOR) has a significant impact on the prognosis. However, total resection is not possible in up to 65% of cases because these tumors frequently infiltrate eloquent areas such as language or motor centers. Consequently, an optimal oncologic result from the surgical perspective cannot be achieved in a considerable large amount of patients. One possible solution is based on the tumor-induced shift of functional areas, which can move away from their original localization. Earlier studies already described the resection of glioma residuals during a second surgery after plastic reorganization has taken place. The authors complained that this reorganization is not detectable without surgery. Navigated transcranial magnetic stimulation (nTMS) was developed for the noninvasive localization of motor and language areas, which enables us to detect the spatial shift of cortical motor and language functions in tumor patients. Recent publications were already able to demonstrate that the individual and exact localization of the motor cortex leads to an increased EOR and prolongs the progression-free survival (PFS). Therefore, the current project intends to take advantage of this plastic reorganization for EOR optimization in cerebral parenchyma tumors. In this context, nTMS is supposed to also induce this plasticity within the frame of a repetitive stimulation protocol (rTMS). Besides other therapeutic applications, rTMS also showed a positive effect on the improvement of aphasia as well as motor recovery in patients after stroke, even in randomized multicenter studies, by inducing plastic reorganization. Moreover, rather than waiting for tumor-induced plastic reorganization, the investigators also aim to use the potential of rTMS for spatial plastic reorganization of functional areas adjacent to intracerebral parenchymal tumors to move functionally eloquent brain regions away from the planned resection cavity.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sandro M Krieg, MD, MBA; Phone Number: +49 89 4140 2151; Email: sandro.krieg@tum.de
• Study Contact Backup: Name: Sebastian Ille, MD; Phone Number: +49 89 4140 2151; Email: sebastian.ille@tum.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • Department of Neurosurgery
      • Contact: Sandro M Krieg, MD, MBA; Phone Number: +49 89 4140 2151; Email: sandro.krieg@tum.de
      • Contact: Sebastian Ille, MD; Phone Number: +49 89 4140 2151; Email: sebastian.ille@tum.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Intracerebral tumor
• Cortical function is located within planned resection area as confirmed by preoperative navigated transcranial magnetic stimulation and/or intraoperative direct electrical stimulation mapping
• Informed consent for participation
• Age >18 years

Exclusion Criteria:

• Prognosis less than 6 months
• Contraindications for MRI or nTMS (cardiac pacemaker, deep brain stimulator, cochlea implant
• Karnofsky-performance-index <60%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Therepeutic; rTMS

Device: Navigated repetitive transcranial magnetic stimulation; In these patients we will apply the following protocol: after the initial nTMS mapping of the according function, patients will be stimulated on 20 consecutive days by a series of rTMS pulses. The frequencies (1-20 Hz), number of pulses (100-1,000), and stimulation intensities (50-130% resting motor threshold = rMT = individual lowest stimulation intensity that evokes positive muscle responses) will be applied in dependency of the individual patients comfort and the evoked effect. Stimulations will be applied to the eloquent brain region, which is infiltrated by the tumor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical location of function (nTMS)	Location of cortical motor or language function as measured by navigated transcranial magnetic stimulation (nTMS) mapping	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical location of function (rsfMRI)	Location of cortical motor or language function as measured by resting state functional MRI (rsfMRI)	3 months
Cortical location of function (DES)	Location of cortical motor or language function as measured by intraoperative direct electrical stimulation (DES)	3 months
Cortical location of function (nTMS / rsfMRI / DES)	Location of cortical motor or language function as measured by nTMS, rsfMRI, and /or DES	6 months
Cortical location of function (nTMS / rsfMRI / DES)	Location of cortical motor or language function as measured by nTMS, rsfMRI, and /or DES	9 months
Cortical location of function (nTMS / rsfMRI / DES)	Location of cortical motor or language function as measured by nTMS, rsfMRI, and /or DES	12 months

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Sandro M Krieg, MD, MBA, Technical University of Munich

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2020
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 404/18 S-AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After confirmation by the local ethics committee, individual participant data that underlie the results reported in the manuscript will be available for investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.
• IPD Sharing Time Frame: Data will be available after deidentification, beginning nine months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Data will be available for individual participant data meta-analysis. Requestors will need to sign a data access agreement. Information regarding submitting proposals and accessing data will be published. Data will be made available by contacting the corresponding author of this manuscript via email.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No