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NCT Number: NCT06381726

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

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

Impact On Cancer Results will increase the achievement of GTR/STR, preserving motor integrity, with dramatic impact on LGGs natural history.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

IRCCS Ospedale Galeazzi Sant'Ambrogio

Milan, Lombardy, 20157, Italy

Location status: Recruiting

Location contact

Lorenzo Bello, MD

CONTACT

[email protected]

0039-340-217-1453

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

(ARM 1):

  • 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

Inclusion criteria

(ARM 2/3/4):

  • 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

Exclusion criteria

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

Treatment and study plan

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

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

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

Primary outcomes

  1. Muscle power

    Time frame: 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

    MRC Muscle power assessment (0-5)

  2. Motor praxia

    Time frame: 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

    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)

Secondary outcomes

  1. Comprehensive neuropsychological assessment

    Time frame: 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

    Language: Naming test; Fhonemic and Semantic Fluency Verbal and Spatial Memory: 15 Rey's Words; Recall Rey figure; Visuo-spatial test: Rey's Copy; Cancellation Test Attention and Executive Functions: Attentive matrice and Trail Making test For each listed test, equivalent score, from 0 to 4, is used.

    Mood Disorders. HADS test (score 0-21 : 0-7= Normal; 8-21 Mood disorders

Study contacts

Contact information is provided by the study sponsor or research team.

Lorenzo Bello, MD

CONTACT

[email protected]

0039-340-217-1453

Sponsors and collaborators

Lead sponsor

University of Milan

Other

Collaborators

  • University of Turin, Italy

Registry information

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Apr 24, 2024
Registry last updated
Apr 24, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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