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

NCT07471100 | Not Yet Recruiting DMC

• 1 other identifier: Protocol n.4/2024 bis
• Study Type: interventional
• Target: 63
• Locations: 0 countries
• Sites: N/A

Brief Summary

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. 1.Does CIM (with or without rTMS) produce measurable motor-cortex plasticity from baseline to pre-surgery as assessed by neuronavigated TMS (nTMS)?
2. 2.Does adding rTMS to CIM lead to greater neuroplastic changes than CIM alone?
3. 3.What clinical, radiological, and neurophysiological outcomes are observed after surgery in participants who receive prehabilitation compared with controls?
4. 4.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)
5. 5.Undergo planned tumor surgery (according to standard methods of care) and complete postoperative clinical, imaging, and neurophysiological follow-up assessments.

Conditions

Brain Tumor Adult; Glioma; Glioma, High Grade

Keywords

prehabilitation; neuromodulation; brain plasticity; cortical plasticity; rTMS; nTMS; physical therapy

Outcome Measures

Primary Outcomes (2)

• Measurement of neuroplasticity with nTMS

  Cortical changes in motor representations will be addressed with Neuronavigated TMS mapping of the motor representations (MEP amplitude and waveforms) of the cortical surface of the peri-Rolandic region on individual anatomical images (Nextim NBS System 5 in Bolzano/EbNeruo STM9000 in Verona). We will consider as primary outcome variable the extension of the cortical surface from which MEPs can be obtained by neuronavigated TMS on the affected hemisphere during the procedure of neuronavigation. This index will be calculated quantitatively as surface area, on the flattened cortical surface, and on the "density" of MEP amplitude on such surface. In addition, we will carry out a quantitative analysis of how many excitable points are present in different cortical regions, by applying the cortical atlas by Glasser et al. (2016) to the patient's brain. In this way we will also be able to quantify the extension of excitable points to the premotor or even non-motor cortical regions.

  From the date of randomization until the date of surgery, assessed up to 15 days

• Measurement of neuroplasticity with TMS

  1. Single-pulse indexes of motor cortical excitability (unit of measure milli Volt - mV): * Cortical Silent Period (CSP) * Recruitment (input-output) Curve (RC) * Resting Motor Threshold (rMT) and intehemispheric rMT ratio (rMT ratio) 2. Dual-pulse measures of cortical excitability (Adimensional; they are MEP-derived ratios . MEP amplitudes are measured in mV).): * Short-latency intracortical inhibition/facilitation (SICI and SICF) * Short-latency afferent inhibition (SAI)

  From the date of randomization until the date of surgery, assessed up to 15 days

Secondary Outcomes (2)

• Measurement of neuroplasticity with TMS (after surgery)

  At 1 month and 3 months after surgery

• Measurement of neuroplasticity with TMS

  At 1 month and 3 months after surgery

Other Outcomes (6)

• Radiological outcome

  From date of randomization until 3 months after surgery

• Clinical Outcome

  From date of randomization until 3 months after surgery

• Clinical Outcome

  From date of randomization until 3 months after surgery

Study Arms (3)

Control (no NICP)

NO INTERVENTION

Physical Therapy Group

Physical Therapy Group: patients who undergo only physical therapy

EXPERIMENTAL

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)

Procedure: Physical Therapy

Combined Therapy Group: patients who undergo physical therapy + rTMS

EXPERIMENTAL

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 focused exercises (e.g. 9-hole peg test) on the controlateral hand (affected side)

Procedure: Combined Therapy Group

Interventions

Physical Therapy PROCEDURE

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)

Physical Therapy Group: patients who undergo only physical therapy

Combined Therapy Group PROCEDURE

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 focused exercises (e.g. 9-hole peg test) on the controlateral hand (affected side)

Combined Therapy Group: patients who undergo physical therapy + rTMS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Refusal to Study participation
• Multifocal/Bilateral Disease

Sponsors & Collaborators

• Azienda Sanitaria dell'Alto Adige: lead
• Università degli Studi di Trento: collaborator
• Azienda Ospedaliera Universitaria Integrata Verona: collaborator

Related Publications (6)

• Boccuni L,Roca-Ventura A,Buloz-Osorio E,Leno-Colorado D,Delgado-Gallén S,Cabello-Toscano M,Perellón-Alfonso R,Villalba-Martínez G,Martínez-Ricarte F,Martín-Fernández J,Buxeda-Rodriguez M,Conesa-Bertrán G,Illueca-Moreno M,Lladó-Carbó E,Perla Y Perla C,Garrido C,Pariente JC,Laredo C,Muñoz-Moreno E,Bargalló N,Trompetto C,Marinelli L,Bartrés-Faz D,Abellaneda-Pérez K,Pascual-Leone A,Tormos-Muñoz JM

  RESULT

• Gulrandhe P,Acharya S,Patel M,Shukla S,Kumar S

  RESULT

• Sheng R,Chen C,Chen H,Yu P

  RESULT

• de Almeida CC,Neville IS,Hayashi CY,Gomes Dos Santos A,Brunoni AR,Teixeira MJ,Paiva WS

  RESULT

• Hamer RP,Yeo TT

  RESULT

• Cargnelutti E,Ius T,Skrap M,Tomasino B

  RESULT

MeSH Terms

Conditions

Glioma

Interventions

Physical Therapy Modalities

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Rehabilitation

Study Officials

• Pier Paolo Berti, MD

  Department of Neurosurgery, Hospital of Bolzano (SABES-ASDAA) - L. Boehler street n5 Bolzano, BZ, Italy 39100

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pier Paolo Berti, MD, PhD(c)

CONTACT

+39 0471439716; pierpaolo.berti@sabes.it

Luigi Cattaneo, Associate professor

CONTACT

+39 0464 808773; luigi.cattaneo@unitn.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: This is a multi-center, prospective, randomized pilot trial. The patients are randomized in 3 groups (eandomization 1:2:2): A. Control Group, B. Physical Therapy Group, C. Physical Therapy+rTMS Group

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2030
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years after the publication of results
• Access Criteria: Access will be provided to qualified researchers who submit a methodologically sound proposal. Approved requestors will be granted access to de-identified IPD underlying the published results, the data dictionary/codebook, and the statistical analysis code. Requests should be sent by email to the study sponsor/principal investigator and will be reviewed by a data access committee (or the study team). Access will be provided after signing a data use agreement and only for the purpose approved in the proposal.