Glucosinolates (GLs) are phytocompounds mainly found in the Cruciferae (Brassicacea) and Moringa oleifera plants. The hydrolysis of GLs by myrosinase led to the production of isothiocyanate (ITCs). ITCs consumption was associated with different health promoting effects, including to neuroprotective, anti-oxidant and anti-inflammatory capacities. In particular, they showed neuroprotective effects in experimental models of neurodegenerative diseases, including multiple sclerosis (MS) and Parkinson's disease (PD). From different GLs, different ITCs are originated. In particular, from glucoraphanin (GRA) the ITC sulforaphane (SFN) is obtained. The PI of the project is one of the proprietor of a patent (EP2908850B1) for the application of (Rs)-GRA with myrosinase in a buffered solution for the treatment of neurodegenerative diseases. The aim of this project is to evaluate the effects of the administration of bioactivated GRA in different cohorts of adult patients, affected by MS and PD, but also a cohort of pediatric patients affected by neuromuscolar and degenerative diseases. The effects of bioactivated (Rs)-GRA administration will be evaluated with a combination of clinical evaluations and a multiomic (metabolomic, genomic) approach.
Male or female patients aged between 45-75 years old.
Clinical diagnosis of PD according to UK Brain Bank Criteria.
3 months of clinical stability before study enrolment.
Anti-parkinsonian medication is fixed for at least 3 months prior to study entry.
Absolute contraindications to Magnetic Resonance Imaging (MRI).
Concomitant neurological disease or severe co-morbidities able to influence outcomes such as spinal injury, cancer, dementia, or other central nervous system diseases such as stroke, epilepsy or psychiatric disorders;
Total score of Mini-Mental State Examination (MMSE)<24.
Participating in other clinical trials.
Parallel
bioactivated GRA for adult patients
Drugadult dose: 50 mg/day of bioactivated GRA for 6 months
bioactivated GRA for pediatric patients
Drugpediatric dose: 10 mg/day of bioactivated GRA for 6 months
6
Treatment groupsSee each treatment group below.
Unified Parkinson's Disease Rating Scale (UPDRS) Total Score
The score ranges from 0 to 260, with 0 indicating no disability and 260 indicating total disability. The scale is divided into four parameters: 0 (normal), 1 (mild), 2 (mild), 3 (moderate), and 4 (severe).
Hoehn and Yahr scale
Parkinson's Disease Progression Stage Scale (Stage 1 to 5). The scale is a subset of the Unified Parkinson's Disease Rating Scale, which allows for a more nuanced assessment of daily activities and non-motor symptoms in the context of disease therapy.
Expanded Disability Status Scale (EDSS) for Multiple Sclerosis patients
Evaluation of the degree of neurological disability in Multiple Sclerosis. The range of the EDSS Step includes 20 half steps from 0 to 10, with EDSS Step 0 corresponding to a completely normal examination and EDSS Step 10 to death due to MS
Cognitive and Neuropsychological Assessments: Montreal Cognitive Assessment (MoCA) and Mini-mental state examination
The MoCA is a one-page 30-point test administered in approximately 10 minutes to dectect cognitive impairment. Scores range between 0 and 30, a score of 26 or over is considered to be normal. The mini-mental state examination (MMSE) or Folstein test is a 30-point test to identify cognitive impairment. Any score of 24 or more (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment. The raw score may also need to be corrected for educational attainment and age
Changes in growth parameters, anthropometric measurements and pubertal status.
Evaluation of physical development and nutritional status. The following parameters will be measured: body weight (kg), height (cm), Body Mass Index (BMI, calculated as weight in kilograms divided by height in meters squared), and their respective percentiles adjusted for age, sex, and specific pathology. These measurements aim to assess the impact of the administration of the study composition on growth and development in the pediatric population. Additionally, pubertal development will be assessed using the Tanner Stage (Sexual Maturity Rating), which evaluates the progression of secondary sexual characteristics (breast development in girls, genital development in boys, and pubic hair in both) on a scale from 1 (pre-pubertal) to 5 (adult). This combined assessment aims to monitor the global growth trajectory and hormonal-physical maturation during the treatment.
Changes in Electroencephalogram (EEG) Mean Frequency and Brain Electrical Activity.
Evaluation of cerebral electrical activity using the Micromed Brain Quick System (System Plus Evolution software) with a 48-channel recording head. Recordings will follow the International 10-20 system (or reduced electrode sets for infants \< 40 cm). The signal will be processed with a sampling frequency of 256 Hz, a high-pass filter of 1.6 Hz, a low-pass filter of 30 Hz, and a sensitivity of 100 μV/cm. Assessments will include wakefulness, sleep deprivation, and afternoon rest. For patients with severe neurological conditions, video-EEG and polygraphy will be associated. The analysis focuses on background activity evolution and paroxysmal abnormalities according to ILAE guidelines.Unit of Measure: Qualitative and Quantitative neurophysiological parameters (presence/absence of epileptiform activity and mean frequency in Hz.
Assessment of Swallowing Function via Dysphagia Outcome and Severity Scale (DOSS) in pediatric patients.
Evaluation of the severity of dysphagia (swallowing impairment). The DOSS is a 7-point scale used to systematically rate functional longitudinal changes in swallowing. Scores range from 1 (Severe dysphagia: nothing by mouth) to 7 (Normal in all situations).
Changes in Psychomotor Development via Griffiths Mental Development Scales 3 (GMDS-3)
The Griffiths-3 Scale (Griffiths III) is a comprehensive developmental assessment for young children (birth to nearly 6 years) that measures mental and physical growth across five key domains: Foundations of Learning, Language \& Communication, Eye \& Hand Coordination, Personal-Social-Emotional, and Gross Motor.Unit of Measure: Developmental Quotient (DQ) score (Standardized score where the mean is 100 and the standard deviation is 15. Higher scores indicate more advanced development).
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IRCCS Centro Neurolesi Bonino Pulejo
Lead sponsor
Fondazione Edmund Mach
Collaborator
Vittore Buzzi Children's Hospital
Collaborator
Azienda Sanitaria Provinciale Ragusa
Collaborator
