Myrosinase Bioactivated Gglucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)

NCT07360977 | Recruiting

• 2 other identifiers: GRA-MYR-NDPNRR-POC-2022-12376049
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PARKINSON DISEASE (Disorder); Multiple Sclerosis (MS) - Relapsing-remitting; Pediatric Patients Affected by Neuromuscolar and Degenerative Diseases

Keywords

phytocompounds; Glucosinolates; isothiocyanate; Parkinson's disease; multiple sclerosis

Outcome Measures

Primary Outcomes (16)

• 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).

  Baseline, 6 months (end of treatment), 12 months

• 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.

  Baseline, 6 months (end of treatment), 12 months

• 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

  Baseline, 6 months (end of treatment), 12 months

• 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

  Baseline, 6 months (end of treatment), 12 months

• Brief Repeatable Battery (BRB) of Neuropsychological Tests for Multiple Sclerosis patients

  THE BRB consists of twelve subtests which give five scores, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, delayed memory). Higher values represent a better outcome.

  Baseline, 6 months (end of treatment), 12 months

• Normalized Brain Volume (NBV)

  Evaluation of global brain atrophy through the measurement of total brain volume normalized for head size using high-field Magnetic Resonance Imaging (MRI). Higher values indicate better brain volume preservation, while a decrease over time indicates progression of brain atrophy.

  Baseline, 6 months (end of treatment), 12 months

• Normalized Cortical Volume (NCV)

  Evaluation of regional atrophy focusing on the cerebral cortex. Measurement of cortical gray matter volume normalized for head size using high-field MRI. This parameter is used to quantify the loss of cortical tissue specifically.

  Baseline, 6 months (end of treatment), 12 months

• Change from Baseline in Whole-Brain Fractional Anisotropy (FA) in Multiple Sclerosis Patients

  FA is a DTI-derived metric that reflects the microstructural integrity of white matter. In Multiple Sclerosis, a reduction in FA values is a marker of axonal damage and demyelination, even in Normal Appearing White Matter (NAWM).The unit of measurement is the Ratio (Scale from 0 to 1, where 1 indicates maximum diffusion/directional integrity.

  Baseline, 6 months (end of treatment), 12 months

• Change from Baseline in Whole-Brain Mean Diffusivity (MD) in Multiple Sclerosis patients

  MD measures the average magnitude of water diffusion. An increase in MD values in MS patients indicates loss of structural barriers, typically due to neurodegeneration, inflammation, or loss of myelin. This parameter provides a global index of tissue destruction.

  Baseline, 6 months (end of treatment), 12 months

• Non-Motor Symptoms Scale (NMSS) for Parkinson patients

  It assesses 30 non motor symptoms across 9 domains, with scores ranging from 0 (no symptoms) to 12 per group (severity x frequency), resulting in a total score of 0 to 360, indicating the extent of the non-motor symptom burden. Lower score indicate fewer symptoms; a negative change from baseline indicates improvement in symptoms. Mean scores vary with disease severity, reflecting increased problems with sleep disturbances, mood, cognition, gastrointestinal function, etc.

  Baseline, 6 months (end of treatment), 12 months

• Quality of Life Assessment: Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Rating Scale.

  Depression severity is assessed using the 17-item Hamilton Rating Scale for Depression (HRSD). Based on the total score, participants will be classified into the following levels: no depression (0-7), mild depression (8-13), moderate depression (14-18), severe depression (19-22), and very severe depression (≥23). The Hamilton Anxiety Rating Scale (HAM-A) is a psychological questionnaire to evaluate the anxiety. The Hamilton Anxiety Rating Scale (HAM-A), which consists of 14 items, each rated on a 5-point scale. The total score, obtained by adding the individual items, ranges from 0 to 56. A score ≤17 indicates mild anxiety; 18-24 indicates mild to moderate anxiety; 25-30 indicates moderate to severe anxiety.

  Baseline, 6 months (end of treatment), 12 months

• Parkinson's Disease Quality of Life Questionnaire (PDQ-8)

  It is a patient-reported outcome measure consisting of 8 items that assesses health-related quality of life in Parkinson's disease. It includes one representative item for each domain of the original PDQ-39: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and physical discomfort. Participants rate their experiences in the previous month using a 5-point Likert scale (0 = never to 4 = always). The total score is converted into a Summary Index (SI) ranging from 0 to 100, with higher scores indicating poorer health-related quality of life.Summary Index scores were interpreted as follows: 0-20 indicating good quality of life with minimal disease impact, 21-40 mild impairment, 41-60 moderate impairment, 61-80 marked impairment, and 81-100 severe impairment of quality of life.

  Baseline, 6 months (end of treatment), 12 months

• Parkinson's Disease Sleep Scale (PDSS-2)

  The PDSS-2 is a 15-item self-administered questionnaire used to evaluate sleep disturbances and nocturnal symptoms in patients with Parkinson's Disease. It covers various domains including motor symptoms at night, sleep quality, and daytime sleepiness. Each item is scored on a 5-point Likert scale from 0 (never) to 4 (very often). The total score ranges from 0 to 60. A total score ≥ 15-18 is often considered indicative of clinically significant sleep disturbance.

  Baseline, 6 months (end of treatment), 12 months

• Change from Baseline in EuroQol-5D-3L Index Score

  The EQ-5D-3L is a standardized instrument for measuring health-related quality of life. It consists of a questionnaire with 5 item: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. These responses are converted into a single index score (utility value) using a country-specific value set.

  Baseline, 6 months (end of treatment), 12 months

• Clinical Global Impression of Improvement (CGI-I)

  The CGI-I is a clinician-rated scale that assesses how much the patient's illness has improved or worsened relative to a baseline state.It is scored on a 7-point Likert scale: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment

  Baseline, 6 months (end of treatment), 12 months

• Patient Global Impression of Change (PGI-C)

  The PGI-C is a self-reported scale reflecting the patient's belief about the efficacy of treatment and their overall change in health status since the start of the study. It uses a 7-point scale where: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.

  Baseline, 6 months (end of treatment), 12 months

Secondary Outcomes (7)

• Changes in growth parameters, anthropometric measurements and pubertal status.

  Baseline, 3 , 6 (end of the treatment) , and 12 months

• Changes in Electroencephalogram (EEG) Mean Frequency and Brain Electrical Activity.

  Baseline, 3, 6 ( end of the treatment), 12 months

• Assessment of Swallowing Function via Dysphagia Outcome and Severity Scale (DOSS) in pediatric patients.

  baseline and 3, 6, 12 months

• Changes in Psychomotor Development via Griffiths Mental Development Scales 3 (GMDS-3)

  baseline and 3, 6, 12 months.

• Pediatric Esophageal Motility and Dysphagia Assessment via High-Resolution Manometry (HRM).

  baseline and 3, 6 ( end of the treatment), 12 months

Study Arms (6)

PD patients receiving only standard therapy

NO INTERVENTION

Patients affected by Parkinson's disease receiving only standard therapy

PD patients receiving bioactivated GRA

EXPERIMENTAL

Patients affected by Parkinson's disease receiving bioactivated GRA

Drug: bioactivated GRA for adult patients

MS patients receiving only standard therapy

NO INTERVENTION

Patients affected by multiple sclerosis receiving only standard therapy

MS patients receiving bioactivated GRA

EXPERIMENTAL

Patients affected by multiple sclerosis receiving bioactivated GRA

Drug: bioactivated GRA for adult patients

Pediatric patients receiving only standard therapy

NO INTERVENTION

Pediatric patients receiving only standard therapy

Pediatric patients receiving bioactivated GRA

EXPERIMENTAL

Pediatric patients receiving bioactivated GRA

Drug: bioactivated GRA for pediatric patients

Interventions

bioactivated GRA for adult patients DRUG

adult dose: 50 mg/day of bioactivated GRA for 6 months

MS patients receiving bioactivated GRA; PD patients receiving bioactivated GRA

bioactivated GRA for pediatric patients DRUG

pediatric dose: 10 mg/day of bioactivated GRA for 6 months

Pediatric patients receiving bioactivated GRA

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged between 45-75 years old.
• Clinical diagnosis of PD according to UK Brain Bank Criteria.
• months of clinical stability before study enrolment.
• Anti-parkinsonian medication is fixed for at least 3 months prior to study entry.
• Male or female patients 18 years old or older.
• Diagnosis of RR-MS according to McDonald criteria.
• Expanded Disability Status Scale(EDSS) lower or equal to 5.5.
• Stable disease for at least 30 days prior to study entry.
• Stable disease-modifying therapy for at least 3 months prior to study entry.
• No changes in drug treatment during 6 months-study treatment.
• Patients understand and comply with the study procedure and are able to complete tests and examinations required by the project.
• Written informed consent.
• Eligible patients are those clinically stable;
• Age range from 1 to 10, between 5 and 30 kg.
• Patients not involved in other clinical trials.

You may not qualify if:

• 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.
• Pregnant/lactating.

Sponsors & Collaborators

• IRCCS Centro Neurolesi Bonino Pulejo: lead
• Fondazione Edmund Mach: collaborator
• Vittore Buzzi Children's Hospital: collaborator
• Azienda Sanitaria Provinciale Ragusa: collaborator

Study Sites (1)

IRCCS Centro Neurolesi Bonino Pulejo

Messina, 98124, Italy

RECRUITING

Related Publications (9)

• Deuschl G, Beghi E, Fazekas F, Varga T, Christoforidi KA, Sipido E, Bassetti CL, Vos T, Feigin VL. The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017. Lancet Public Health. 2020 Oct;5(10):e551-e567. doi: 10.1016/S2468-2667(20)30190-0.

  PMID: 33007212 BACKGROUND

• Klomparens EA, Ding Y. The neuroprotective mechanisms and effects of sulforaphane. Brain Circ. 2019 Apr-Jun;5(2):74-83. doi: 10.4103/bc.bc_7_19. Epub 2019 Jun 27.

  PMID: 31334360 BACKGROUND

• Yadav SK, Soin D, Ito K, Dhib-Jalbut S. Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis. J Mol Med (Berl). 2019 Apr;97(4):463-472. doi: 10.1007/s00109-019-01761-5. Epub 2019 Feb 28.

  PMID: 30820593 BACKGROUND

• Kamal RM, Abdull Razis AF, Mohd Sukri NS, Perimal EK, Ahmad H, Patrick R, Djedaini-Pilard F, Mazzon E, Rigaud S. Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases. Molecules. 2022 Jan 19;27(3):624. doi: 10.3390/molecules27030624.

  PMID: 35163897 BACKGROUND

• Schepici G, Bramanti P, Mazzon E. Efficacy of Sulforaphane in Neurodegenerative Diseases. Int J Mol Sci. 2020 Nov 16;21(22):8637. doi: 10.3390/ijms21228637.

  PMID: 33207780 BACKGROUND

• Lotti C, Rubert J, Fava F, Tuohy K, Mattivi F, Vrhovsek U. Development of a fast and cost-effective gas chromatography-mass spectrometry method for the quantification of short-chain and medium-chain fatty acids in human biofluids. Anal Bioanal Chem. 2017 Sep;409(23):5555-5567. doi: 10.1007/s00216-017-0493-5. Epub 2017 Jul 17.

  PMID: 28717897 BACKGROUND

• Garcia-Aloy M, Ulaszewska M, Franceschi P, Estruel-Amades S, Weinert CH, Tor-Roca A, Urpi-Sarda M, Mattivi F, Andres-Lacueva C. Discovery of Intake Biomarkers of Lentils, Chickpeas, and White Beans by Untargeted LC-MS Metabolomics in Serum and Urine. Mol Nutr Food Res. 2020 Jul;64(13):e1901137. doi: 10.1002/mnfr.201901137. Epub 2020 Jun 22.

  PMID: 32420683 BACKGROUND

• Ulaszewska, M.M., Trost, K., Stanstrup, J. et al. Urinary metabolomic profiling to identify biomarkers of a flavonoid-rich and flavonoid-poor fruits and vegetables diet in adults: the FLAVURS trial

  BACKGROUND

• Anesi A, Berding K, Clarke G, Stanton C, Cryan JF, Caplice N, Ross RP, Doolan A, Vrhovsek U, Mattivi F. Metabolomic Workflow for the Accurate and High-Throughput Exploration of the Pathways of Tryptophan, Tyrosine, Phenylalanine, and Branched-Chain Amino Acids in Human Biofluids. J Proteome Res. 2022 May 6;21(5):1262-1275. doi: 10.1021/acs.jproteome.1c00946. Epub 2022 Apr 5.

  PMID: 35380444 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Emanuela Mazzon

  IRCCS Centro Neurolesi Bonino Pulejo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emanuela Mazzon

CONTACT

09060128163; emanuela.mazzon@irccsme.it

Study Design

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

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: January 22, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): May 19, 2026
• Study Completion (Estimated): May 19, 2026
• Last Updated: January 22, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)