Multiple Sclerosis Relapse Clinical Trial
Official title:
An Observation Monocentric Study to Analyse the Possible Neuroprotective Effect of Ocrelizumab Via VEGF Protein Expression in Relapsing Multiple Sclerosis Patients
Ocrelizumab (OCR) is a humanized anti-CD20 antibody approved for Relapsing Multiple Sclerosis (RMS) and Primary Progressive Multiple Sclerosis (PPMS), due to neuroprotective effects of partially unknown origin. While its mechanism of action is mainly thought to occur via B cell depletion, previous studies on rituximab, another anti-CD20 drug, showed that CD20 binding elicits several intracellular signalling pathways, also including Protein Kinase C (PKC) activation. Of interest, the β isoform of PKC is known to modulate, through the RNA-binding protein ELAV/HuR, the expression of Vascular Endothelial Growth Factor (VEGF), a signaling protein that has been suggested to play deleterious effects in the first phases of MS. Therefore, the hypothesis is that part of the neuroprotective effects exerted by OCR may also be due to the modulation of VEGF expression via PKCβ /HuR cascade. The primary objective is to evaluate the variation of the expression of VEGF (protein and mRNA) in Peripheral Blood Mononuclear Cells (PBMCs) induced by OCR therapy. No additional visits will be required outside of clinical practice. Additional laboratory testing (VEGF protein expression and PKCbeta/HuR cascade) will be performed on extra blood which will be taken during the routine blood exams. This study is an observational, longitudinal, monocenter and single arm study, in patients with RMS who are newly prescribed with OCR as per clinical practice. The study consists of the following visits as per clinical practice - T0 visit: at the first dose of OCR, blood sample and clinical/radiological MS data will be collected. - T6: after 6 months of OCR treatment, blood samples and clinical MS data will be collected. - T12 visit: after 12 months of OCR treatment, blood samples and clinical MS data will be collected.
Status | Not yet recruiting |
Enrollment | 21 |
Est. completion date | July 31, 2024 |
Est. primary completion date | July 31, 2024 |
Accepts healthy volunteers | |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility | Inclusion criteria - The participant must have a previous diagnosis of RMS in accordance with the 2017 revised McDonald criteria - The participant must have been newly prescribed to OCR treatment according to clinical practice - Absence of high dose of steroid treatment for at least 4 weeks - The participant must be capable of giving signed informed consent. Exclusion criteria - Clinical MS relapse within four-week period prior to inclusion - Pregnant or nursing (lactating) women. - Chronic disease of the immune system, other than MS - Active systemic bacterial, viral or fungal infections - Allergy to OCR - Already included in other interventional trials |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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IRCCS National Neurological Institute "C. Mondino" Foundation |
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* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
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Primary | VEGF protein levels | To evaluate the expression of VEGF protein in PBMCs from patients with RMS | Month 12 versus baseline (T0) | |
Secondary | VEGF protein levels | To evaluate the expression of VEGF protein in PBMCs from patients with RMS before and after OCR treatment. | Month 6 versus baseline (T0) | |
Secondary | VEGF mRNA levels | To evaluate the expression of VEGF mRNA in PBMCs from patients with RMS before and after OCR treatment | Change from baseline (T0) to Month 6 and Month 12 | |
Secondary | PKCß protein levels | To evaluate the expression of PKCß protein in PBMCs from patients with RMS before and after OCR treatment | Change from baseline (T0) to Month 6 and Month 12 | |
Secondary | PKCß mRNA levels | To evaluate the expression of PKCß mRNA in PBMCs from patients with RMS before and after OCR treatment | Change from baseline (T0) to Month 6 and Month 12 | |
Secondary | Expanded Disability Status Scale (EDSS) | To evaluate whether the expression of VEGF and PKCß affects MS severity before and after OCR treatment.
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. |
Change from baseline (T0) to Month 6 and Month 12 | |
Secondary | Multiple Sclerosis Severity Score (MSSS) | To evaluate whether the expression of VEGF and PKCß affects MS severity before and after OCR treatment.
The Multiple Sclerosis Severity Score (MSSS) relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations. |
Change from baseline (T0) to Month 6 and Month 12 |
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