Personalized Rendering of Motor System Functional Plasticity Potential to Improve Glioma Resection and Quality of Life
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Milan
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Age <18 years
Inability to adhere to standard study controls
Subjects unable to understand and freely provide consent to the study
Trial design
Design model
Parallel
Treatments tested in this trial
Resting State Functional Magnetic Resonance Imaging (rs-fMRI)
Diagnostic testrs-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
Behavioralpersonalized 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
DrugTemozolomide 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
Treatment groups
400 Participants
are divided into 4 treatment groupsGroup A: Spontaneous motor reorganization: observationActive comparator 1 intervention
Group B: Enhanced motor reorganization: upfront Motor RehabilitationExperimental treatment 1 intervention
Group C: Enhanced motor reorganization: upfront ChemotherapyExperimental treatment 1 intervention
Group D: Enhanced motor reorganization: upfront Chemotherapy + Motor RehabilitationExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Muscle power
MRC Muscle power assessment (0-5)
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 postop2
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)
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 postopSecondary outcomes
1
Comprehensive neuropsychological assessment
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
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 postopSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Milan
Lead sponsor
University of Turin, Italy
Collaborator
Source ClinicalTrials.gov