Administrative information
Title {1} | Preconditioning of the motor network with repetitive navigated transcranial magnetic stimulation (rnTMS) to improve oncological and functional outcome in brain tumor surgery: a study protocol for a randomized, sham-controlled, triple-blind clinical trial |
Trial registration {2a and 2b}. | The trial was registered at DRKS.de (DRKS00017232) on 28.01.2020. |
Protocol version {3} | Version 1, 12.06.2023 |
Funding {4} | This clinical trial is funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung (BMBF), Deutsches Zentrum für Luft- und Raumfahrt (DLR) Projektträger Gesundheit) by grant number 01KG2302. |
Author details {5a} | Melina Engelhardt: Charité - Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Charitéplatz 1, 10117 Berlin, Germany Melina Engelhardt: Charité - Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Einstein Center for Neurosciences, Charitéplatz 1, 10117 Berlin, Germany Melina Engelhardt: Charité - Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, International Graduate Program Medical Neurosciences, Charitéplatz 1, 10117 Berlin, Germany Ulrike Grittner: Charité - Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biometry and Clinical Epidemiology, Charitéplatz 1, 10117 Berlin, Germany Sandro Krieg: Department of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Thomas Picht: Charité - Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Charitéplatz 1, 10117 Berlin, Germany |
Thomas Picht: Cluster of Excellence Matters of Activity. Image Space Material, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099 Berlin, Germany | |
Name and contact information for the trial sponsor {5b} | Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany |
Role of sponsor {5c} | The funding source {4} and sponsor {5b} had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. |
Introduction
Background and rationale {6a}
Objectives {7}
Primary hypotheses
Secondary hypotheses
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
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Suspected supratentorial glioma grade II-IV in a motor-relevant area based on preoperative (Magnetic Resonance Imaging (MRI)
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Infiltration of primary motor cortex or distance between tumor and corticospinal tract below 8 mm [13] based on results of preoperative nTMS assessment and following tractography of the corticospinal tract
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Study participation does not delay surgery
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Age ≥ 18 years at the time of signing the informed consent
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Ability to give written informed consent subject exclusion criteria
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Contraindications for receiving an MRI as assessed by the attending neuroradiologist
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Contraindications for undergoing a TMS examination as assessed by the attending neurosurgeon
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Surgery scheduled within < 5 days after screening for inclusion criteria
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More than one seizure per week based on patient reports or medical records
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Pregnancy
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Missing informed consent
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Primary endpoints
Secondary endpoints
Participant timeline {13}
Study procedure | Screening | Baseline | Intervention | After intervention | Surgery | 7 days post-operative | 3 months post-operative |
---|---|---|---|---|---|---|---|
Visit number | T0 | T1 | T2 | T3 | |||
Study day | −1 | 0 | 0–5/28 | 5/28 | 6/29 | 13/36 | 3 months |
Informed consent | X | ||||||
Inclusion/exclusion criteria | X | ||||||
Demographics, medical/neurol. history | X | ||||||
nTMS measurement | X | X | |||||
Motor status (BMRC)a | X | X | X | Xa | |||
Structural MRI incl. assessment of GTRa | X | X | Xa | ||||
EORTC-BN20 | X | X | X | X | |||
ARAT | X | X | X | X | |||
Diffusion-weighted MRI | X | ||||||
Resting-state fMRI | X | X | |||||
rnTMS stimulation | X | ||||||
Motor training | X | ||||||
(Serious) adverse eventsb | X | X | X | X | X | X | |
Details of surgery | X | ||||||
Tumor histology | X |