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

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. 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.

Conditions

• Brain Tumor Adult
• Glioma
• Glioma, High Grade

Interventions

PROCEDURE

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)

PROCEDURE

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

Sponsors & Collaborators

• Università degli Studi di Trento

  collaborator OTHER

• Azienda Ospedaliera Universitaria Integrata Verona

  collaborator OTHER

• Azienda Sanitaria dell'Alto Adige

  lead OTHER

Principal Investigators

• Pier Paolo Berti, MD · Department of Neurosurgery, Hospital of Bolzano (SABES-ASDAA) - L. Boehler street n5 Bolzano, BZ, Italy 39100

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-01

Primary Completion

2028-03-31

Completion

2030-03-31