Neuromodulation-Induced Cortical Prehabilitation in High Grade Glioma Near the Motor Pathway: Cortical Plasticity Assessed by Navigated Transcranial Magnetic Stimulation (nTMS)

Официальное название

Neuromodulation-Induced-Cortical-Prehabilitation In High Grade Glioma Close To The Motor Pathway: Analysis Of The Cortical Brain Plasticity Through Navigated Transacranial Magnetic Stimulation

Обзор

The goal of this clinical trial is to learn whether Neuromodulation-Induced-Cortical-Prehabilitation (NICP)-using physical therapy (constraint-induced movement training, CIM) alone or combined with repetitive transcranial magnetic stimulation (rTMS)-can promote motor-cortex neuroplasticity before surgery in adults with high-grade gliomas near the motor pathway. It will also learn about the feasibility and safety of these prehabilitation strategies around the time of surgery. The main questions it aims to answer are: 1. Does CIM (with or without rTMS) produce measurable motor-cortex plasticity from baseline to pre-surgery as assessed by neuronavigated TMS (nTMS)? 2. Does adding rTMS to CIM lead to greater neuroplastic changes than CIM alone? 3. What clinical, radiological, and neurophysiological outcomes are observed after surgery in participants who receive prehabilitation compared with controls? Researchers will compare standard care (control) vs CIM-based physical therapy vs CIM plus rTMS to see if these approaches induce preoperative neuroplastic changes that may support better surgical outcomes. Participants will: 1. Be randomized to one of three groups: control, CIM physical therapy, or CIM + rTMS• Undergo nTMS motor mapping and excitability testing at baseline (T0) and the day before surgery (T1) 2. Undergo planned tumor surgery (according to standard methods of care) and complete postoperative clinical, imaging, and neurophysiological follow-up assessments.

Подробное описание

Background. The Neuromodulation-Induced-Cortical-Prehabilitation (NICP) is a groundbreaking idea to promote plastic brain changes and, theoretically, to increase the Extent of Resection in brain gliomas improving the surgical outcomes. Moreover, given the infiltrative nature of brain gliomas, NICP could be consistently worthwhile for the patient's clinical outcome, reducing the likelihood of premeditated neurologic sequelae and/or the time-to-recovery during the post-surgical rehabilitation.

Hypothesis, Research Need. Up to date only small case series have analysed NICP-induced neuroplasticity, complicating data interpretation. Our study aims to thoroughly measure through neuronavigated Transcranial-Magnetic-Stimulation (nTMS) the plastic brain changes of Physical Therapy (in particular Constraint-Induced-Movements - CIM), repetitive-TMS (rTMS) and the combination of these two techniques in high-grade gliomas (HGGs) close to the motor pathway before surgery to improve surgical outcomes for the benefit of the patient.

Methodology. This is a multi-center, prospective, randomized pilot trial. The patients are randomized in 3 groups (A. Control Group, B. Physical Therapy Group, C. Physical Therapy+rTMS Group; randomization 1:2:2). The participants undergo motor cortex analysis through nTMS at the baseline - T0 - and the day before surgery - T1. Postoperative clinical, radiological and neurophyisiological outcomes are also gathered.

Patient Enrolment:

* Department of Neurosurgery, Hospital of Bolzano (SABES-ASDAA), Bolzano, Italy * Department of Neurosurgery, Azienda Ospedaliera Universitaria Integrata (AOUI) di Verona, Italy

Data analysis:

* Department of Neurosurgery, Hospital of Bolzano (SABES-ASDAA), Bolzano, Italy * Center for Mind/Brain Sciences - CIMEC, University of Trento, Italy * Department of Neurorehabilitation, Hospital of Vipiteno, SABES-ASDAA), Vipiteno, Italy

Analysis Tools:

1. Measurement of neuroplasticity with TMS(Nextim NBS System 5 in Bolzano/EbNeruo STM9000 in Verona). Cortical changes in motor representations will be addressed with:a) nTMS mapping of the motor cortex representations (MEP amplitude and waveforms) on individual anatomical imagesb) 2. Single-pulse indexes of motor cortical excitability:

* Cortical Silent Period * Recruitment Curve * Resting Motor Threshold (and intehemispheric ratio) 3. Dual-pulse measures of cortical excitability:

* Short-latency intracortical inhibition/facilitation * Short-latency afferent inhibition

Expected Outcomes. The investigators don't expect any variation in cortical neuroplasticity between T0 and T1 in group A. On the contrary, The investigators expect a variation in group B, in group C and in group B vs. C.

Вмешательства

• Процедура Physical Therapy
  Physical Therapy protocol for the 10 days preceding surgery: 6h/day Constraint Induced Movement - CIM (immobilization of the ipsilesional hand - unaffected side) + 1h twice a day of fine motor skills focused exercises (e.g. 9-hole peg test) on the controlateral hand (affected side)
• Процедура Combined Therapy Group
  Repetitive Transcranial Magnetic Stimulation protocol for the 10 days preceding surgery: This will be done following standard protocols mediated from the protocols for motor and language function in stroke, i.e, daily sessions of 1Hz rTMS for 20 minutes applied to the contralesional hemisphere. • Physical Therapy protocol for the 10 days preceding surgery: 6h/day Constraint Induced Movement - CIM (immobilization of the ipsilesional hand - unaffected side) + 1h twice a day of fine motor skills fo

Первичные конечные точки

• Measurement of neuroplasticity with nTMS [Срок оценки: From the date of randomization until the date of surgery, assessed up to 15 days]
• Measurement of neuroplasticity with TMS [Срок оценки: From the date of randomization until the date of surgery, assessed up to 15 days]

Вторичные конечные точки (2)

• Measurement of neuroplasticity with TMS (after surgery) [Срок оценки: At 1 month and 3 months after surgery]
• Measurement of neuroplasticity with TMS [Срок оценки: At 1 month and 3 months after surgery]

Критерии участия

Критерии включения

• Age 18-80
• Suspect of High Grade Glioma in MRI
• Any case of cortical/subcortical HGG radiologically close to Motor Pathway and, thus, where intraoperative monitoring assistance is usually required
• Preservation of motor function (at least ≥ 3 according to Medical Research Council classification)
• Signed informed Consent

Критерии исключения

• Refusal to Study participation
• Multifocal/Bilateral Disease

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Boccuni L, Roca-Ventura A, Buloz-Osorio E, Leno-Colorado D, Delgado-Gallen S, Cabello-Toscano M, Perellon-Alfonso R, Villalba-Martinez G, Martinez-Ricarte F, Martin-Fernandez J, Buxeda-Rodriguez M, Conesa-Bertran G, Illueca-Moreno M, Llado-Carbo E, Perla Y Perla C, Garrido C, Pariente JC, Laredo C, Munoz-Moreno E, Bargallo N, Trompetto C, Marinelli L, Bartres-Faz D, Abellaneda-Perez K, Pascual-Leo PMID 39044115
• Gulrandhe P, Acharya S, Patel M, Shukla S, Kumar S. Pertinence of Constraint-Induced Movement Therapy in Neurological Rehabilitation: A Scoping Review. Cureus. 2023 Sep 13;15(9):e45192. doi: 10.7759/cureus.45192. eCollection 2023 Sep. PMID 37842361
• Sheng R, Chen C, Chen H, Yu P. Repetitive transcranial magnetic stimulation for stroke rehabilitation: insights into the molecular and cellular mechanisms of neuroinflammation. Front Immunol. 2023 May 22;14:1197422. doi: 10.3389/fimmu.2023.1197422. eCollection 2023. PMID 37283739
• de Almeida CC, Neville IS, Hayashi CY, Gomes Dos Santos A, Brunoni AR, Teixeira MJ, Paiva WS. Quantification of tumor induced motor cortical plasticity using navigated transcranial magnetic stimulation in patients with adult-type diffuse gliomas. Front Neurosci. 2023 Mar 15;17:1143072. doi: 10.3389/fnins.2023.1143072. eCollection 2023. PMID 37008212
• Hamer RP, Yeo TT. Current Status of Neuromodulation-Induced Cortical Prehabilitation and Considerations for Treatment Pathways in Lower-Grade Glioma Surgery. Life (Basel). 2022 Mar 22;12(4):466. doi: 10.3390/life12040466. PMID 35454957
• Cargnelutti E, Ius T, Skrap M, Tomasino B. What do we know about pre- and postoperative plasticity in patients with glioma? A review of neuroimaging and intraoperative mapping studies. Neuroimage Clin. 2020;28:102435. doi: 10.1016/j.nicl.2020.102435. Epub 2020 Sep 14. PMID 32980599

Идентификаторы

NCT: NCT07471100 · Protocol n.4/2024 bis

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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