Personalized Rendering of Motor System Functional Plasticity Potential to Improve Glioma Resection and Quality of Life

NCT06381726 | Recruiting

• 1 other identifier: Progetto AIRC IG-2022 ID 27184
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Background Lower-grade-gliomas affect young patients, thus the longest progression-free-survival (PFS) with a high level quality of life is crucial. Surgery most significantly impacts on tumor natural history, postponing recurrence, improving symptoms, decreasing the need of adjuvant therapies, with extent of resection, gross-total and supra-total (GTR and STR), strongly associating with longest PFS. Achievement of GTR or STR depends on the degree of functional reorganization induced by glioma. Consequently, a successful treatment fostering neural circuit reorganization before surgery, would increase the chance of GRT/STR. Hypothesis The plastic potential of motor system suggests that reorganization of circuits controlling hand movements could be presurgically fostered in LGG patients by enhancing plasticity with up-front motor-rehabilitation and/or by decreasing tumor infiltration with up-front chemotherapy. Advanced neuroimaging allows to infer the neuroplasticity potential. Intraoperative assessment of the motor circuits functionality will validate reliability of preoperative analyses. Aims The project has 4 aims, investigating: A) the presurgical functional (FC) and structural (SC) connectomics of the hand-motor network to picture the spontaneous reorganization and the influence of clinical, imaging and histomolecular variables; B) the dynamic of FC and SC after tumor resection; C) changes in FC and SC maps after personalized upfront motor rehabilitation and/or chemotherapy; D) the effect of FC and SC upfront treatment on the achievement of GTR/STR preserving hand dexterity. Experimental Design Resting-state fMRI and diffusion-MRI will provide FC and SC maps pre- and post-surgery; personalized up-front motor rehabilitation and/or chemotherapy will be administered; Intraoperative brain mapping procedures will generate data to validate the maps. Expected Results

1. 1.Provide a tool to render the motor functional reorganization predictive of surgical outcome.
2. 2.Identify demographic, clinical and imaging variables associated with functional reorganization.
3. 3.Describe the gain induced by up-front treatment.
4. 4.Distinguish "patterns" predicting chance for GTR/STR from "patterns" suggesting need for up-front treatment.

Conditions

Glioma; Glioma, Malignant

Keywords

Glioma; Neurosurgery; Chemotherapy, Neoadjuvant; Motor Rehabilitation; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging; Resting State Functional Magnetic Resonance Imaging; Functional Magnetic Resonance Imaging; Functional Connectomics; Structural Connectomics; Neuronal Plasticity; Higher Nervous Activity; Neurological Rehabilitation; Antineoplastic Protocols

Outcome Measures

Primary Outcomes (2)

• Muscle power

  MRC Muscle power assessment (0-5)

  ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop

• Motor praxia

  ARAT test (Grasp, Grip, Pinch, each consisting of 3 items scoring 0 \[not performed, 1/2 abnormal, 3 ok\]), De Renzi test (24 complex gestures with individual scoring 0-3 \[0 no execution/always abnormal, 2/1 ok after 1 or 2 trials, 3 ok\] each evaluating one or more among finger movements \[total score 0-36\], hand movements \[total score 0-36\], hand and finger position \[total score 0-36\], sequence of movements \[total score 0-36\], meaningful gestures \[total score 0-36\], meaningless gestures \[total score 0-36\]; tool pantomime for 10 objects individual score 0 if always incorrect, 1 if correct after command repetition, 2 correct immediately, total score range 0-20)

  ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop

Secondary Outcomes (1)

• Comprehensive neuropsychological assessment

  ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop

Study Arms (4)

Spontaneous motor reorganization: observation

ACTIVE COMPARATOR

Only neurological and neuropsychological assessment as per normal clinical routine and conventional and advanced functional, resting-state MRI acquisitions

Diagnostic Test: Resting State Functional Magnetic Resonance Imaging (rs-fMRI)

Enhanced motor reorganization: upfront Motor Rehabilitation

EXPERIMENTAL

Patients submitted to motor rehabilitation program aimed at learning unimanual and bimanual coordinated sequences, along with personalized exercise according to tumor location (frontal vs parietal). For 6 months each patient will perform the motor training program in outpatient training session, checked by a physiotherapist for corrected execution at home 3 times/week, and is assessed for the correct training execution and progresses in training sessions each month, by physical therapists at the Rehabilitation Unit and on a weekly schedule by on-line distant monitoring (telemedicine).

Behavioral: Up-front Motor Rehabilitation

Enhanced motor reorganization: upfront Chemotherapy

EXPERIMENTAL

Temozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4).

Drug: Up-front Chemotherapy

Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation

EXPERIMENTAL

Temozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4). Patients will also be submitted to motor rehabilitation program aimed at learning unimanual and bimanual coordinated sequences, along with personalized exercise according to tumor location (frontal vs parietal). For 6 months each patient will perform the motor training program in outpatient training session, checked by a physiotherapist for corrected execution at home 3 times/week, and is assessed for the correct training execution and progresses in training sessions each month, by physical therapists at the Rehabilitation Unit and on a weekly schedule by on-line distant monitoring (telemedicine).

Behavioral: Up-front Motor Rehabilitation; Drug: Up-front Chemotherapy

Interventions

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) DIAGNOSTIC_TEST

rs-fMRI + neurological and neuropsychological evaluation at preoperative timepoint and 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop

Spontaneous motor reorganization: observation

Up-front Motor Rehabilitation BEHAVIORAL

personalized motor rehabilitation for 6 months + rs-fMRI + neurological and neuropsychological evaluation before starting motor rehabilitation, at 2-3 months during rehabilitation, 6-9 months during rehabilitation, before surgery (if surgery indicated by tumour board), 1 month postop, 2-3 months postop

Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation; Enhanced motor reorganization: upfront Motor Rehabilitation

Up-front Chemotherapy DRUG

Temozolomide at either 6 cycles consisting of 150-200 mg per square meter for 5 days during each 28-day cycle, or metronomic schedule, + rs-fMRI + neurological and neuropsychological evaluation before starting motor rehabilitation, at 2-3 months during rehabilitation, 6-9 months during rehabilitation, before surgery (if surgery indicated by tumour board), 1 month postop, 2-3 months Post

Enhanced motor reorganization: upfront Chemotherapy; Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation

Eligibility Criteria

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

You may qualify if:

• Patients signing informed consent for participation in the study
• Males and females
• Age ≥ 18 years
• Patients with lower-grade gliomas with involvement of the motor pathways who are candidates for surgery
• Patients signing informed consent for participation in the study
• Males and females
• Age ≥ 18 years
• Patients with lower-grade gliomas treated over two years with tumors only biopsied and/or partially resected and eligible for second surgery

You may not qualify if:

• Age \<18 years
• Inability to adhere to standard study controls
• Subjects unable to understand and freely provide consent to the study

Sponsors & Collaborators

• University of Milan: lead
• University of Turin, Italy: collaborator

Study Sites (1)

IRCCS Ospedale Galeazzi Sant'Ambrogio

Milan, Lombardy, 20157, Italy

RECRUITING

Related Publications (27)

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MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

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

Study Officials

• Lorenzo Bello, MD

  University of Milan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenzo Bello, MD

CONTACT

0039-340-217-1453; lorenzo.bello@unimi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Model Details: Patients immediately candidate for resection will be assessed neurologically, neuropsychologically and by functional MRI. Extent of resection will be assessed on \<48hrs and 2-month MRI. Neurological and neuropsychological assessment will be performed during regular follow-up. Patients not requiring an adjuvant treatment according to tumor board meeting will be submitted to functional MRI at 4-8 and 12 months from surgery. Patients not immediately eligible for resection will be submitted to biopsy for histomolecular definition. Patients not requiring radiation therapy will be submitted to neurological, neuropsychological, and functional MRI evaluation. Upon clinical context, patients will undergo motor rehabilitation and/or chemotherapy. After 3-6 months, patients will undergo functional MRI and evaluated for surgery. Neurological and neuropsychological evaluation will be performed at treatment initiation, every month during treatment, at admission for surgery and 1 month after surgery.

Study Record Dates

• First Submitted: March 28, 2024
• First Posted: April 24, 2024
• Study Start: March 7, 2024
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2028
• Last Updated: April 24, 2024

Record last verified: 2024-04

Locations

IT (1)