Multiple Sclerosis RelapseNCT04902690
The Possible Neuroprotective Effect of Ocrelizumab Via VEGF Protein Expression in Relapsing Multiple Sclerosis Patients
An observational study of Multiple Sclerosis Relapse, run by IRCCS National Neurological Institute "C. Mondino" Foundation.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis Relapse
- How many people
- 21 participants
- Where
- No sites listed yet
- Study dates
- 31 May 2021to 31 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Adult
Study population: Patients with RMS, who are newly prescribed with OCR as per clinical practice, are enrolled.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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.
Read more
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.
Read the detailed description
Ocrelizumab (OCR) is a humanized monoclonal anti-CD20 antibody approved by the FDA in 2017 and by the European Medicines Agency in 2018 for treatment of adult patients with Relapsing Multiple Sclerosis (RMS). In addition, having shown neuroprotective effects, OCR is the first drug ever approved for early treatment of Primary Progressive MS (PPMS). Currently, OCR is thought to mostly act via the rapid depletion of the B cells expressing CD20. Additionally, this depletion most likely causes long-lasting changes in the profile of B cells, characterized by a reduction of their pro-inflammatory phenotype, as demonstrated with other anti-CD20 antibodies.
Of interest, previous studies on other anti-CD20 drugs, mainly rituximab, have shown that anti-CD20 agents also exert interesting effects on additional intracellular signaling pathways, such as those involving serine/threonine and tyrosine kinases, as well as c-myc. Considering the structural, pharmacokinetic and pharmacodynamic similarities between OCR and rituximab, it can be hypothesized that the efficacy of OCR in delaying disease progression and neuroprotection might also stem from such intracellular effects.
Among the various intracellular effects elicited by rituximab through the binding with CD20, stimulation of the Protein Kinase C (PKC) pathway is of potential significance. The term PKC encompasses a family of several serine/threonine protein kinases of which the isoform β has been implicated in pathological processes, such as diabetic retinopathy, via a specific PKCβ/HuR/Vascular Endothelial Growth Factor (VEGF) pathway (Amadio et al. 2010). Notably, HuR belongs to a family of RNA-binding proteins, named ELAV, which are able to influence virtually any aspect of the post-synthesis fate of the targeted transcripts, including VEGF.
VEGF is a signaling molecule involved in vital processes such as angiogenesis, endothelial proliferation and cellular response to hypoxia. The possible role of VEGF in MS pathogenesis and evolution has not been explored until recently, but mounting evidence points to the conclusion that VEGF might play a significant noxious role in the relapsing stage of MS, for instance by mediating an increase in blood-brain barrier (BBB) permeability, while playing a beneficial, neuroprotective role in the late, progressive stage of the disease. Of note, VEGF has a primary role in promoting vascular hyperpermeability, indeed via phosphorylation of endothelial tight junction proteins modulates their degradation, finally leading to BBB disruption. Further, it also regulates vessel growth and is chemotactic for monocytes and lymphocytes, promoting neuroinflammation.
Of interest, a significant increase in VEGF was observed in mice in the acute phase of murine MOG-induced MS, which correlates to the clinical score, and in sera of MS patients during clinical disease relapses.
Based on these considerations, it can be possible that OCR exerts an additional beneficial effect in MS therapy by modulating VEGF content.
With this project, we aim to explore the effects of OCR on intracellular signaling pathways by assessing VEGF expression in Peripheral Blood Mononuclear Cells (PBMCs) of RMS patients at the beginning of OCR therapy, as well as at 6 and 12 months of ongoing treatment.
In particular, ther purpose of the study is to focus on the pro-angiogenic VEGF-A 165, which seems the isoform mainly involved as mediator of inflammation and cellular immunity.
Further, the PKCβ/HuR cascade will be investigated in the same conditions. Secondly, disease activity during OCR treatment will be examined at every step, and also compared with VEGF and PKC levels.
The results will also possibly demonstrate a necessity of further determining the extent and significance of intracellular effects of anti-CD20 therapy in MS.
This study is an observational (phase 4) , 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:
- Baseline/start (T0): informed consent signature, inclusion/exclusion criteria verification, demographical characteristics, clinical medical history recording, concomitant therapies, neurological history recording (MS history), number of relapses from MS onset, neurological examination, the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Severity Score (MSSS), blood sample, ocrelizumab administration.
- T6: (after 6 months of OCR treatment) adverse events (including relapses), neurological examination, therapies changes, EDSS, MSSS, blood sample, ocrelizumab administration.
- T12 (after 12 months* of OCR treatment), adverse events (including relapses), neurological examination, therapies changes, EDSS, MSSS, blood sample, ocrelizumab administration.
- Conditions
- Multiple Sclerosis Relapse
- Keywords
- Neuroprotective effect, Ocrelizumab, Multiple sclerosis, Vascular Endothelial Growth Factor
- Medical subject headings
- Multiple Sclerosis
What is being measured
The primary outcome is the main question the study is designed to answer.
VEGF protein levels
To evaluate the expression of VEGF protein in PBMCs from patients with RMS
Measured: Month 12 versus baseline (T0)
Secondary outcomes (6)
VEGF protein levels
To evaluate the expression of VEGF protein in PBMCs from patients with RMS before and after OCR treatment.
Measured: Month 6 versus baseline (T0)
VEGF mRNA levels
To evaluate the expression of VEGF mRNA in PBMCs from patients with RMS before and after OCR treatment
Measured: Change from baseline (T0) to Month 6 and Month 12
PKCβ protein levels
To evaluate the expression of PKCβ protein in PBMCs from patients with RMS before and after OCR treatment
Measured: Change from baseline (T0) to Month 6 and Month 12
PKCβ mRNA levels
To evaluate the expression of PKCβ mRNA in PBMCs from patients with RMS before and after OCR treatment
Measured: Change from baseline (T0) to Month 6 and Month 12
Expanded Disability Status Scale (EDSS)
To evaluate whether the expression of VEGF and PKCβ 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.
Measured: Change from baseline (T0) to Month 6 and Month 12
Multiple Sclerosis Severity Score (MSSS)
To evaluate whether the expression of VEGF and PKCβ 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.
Measured: Change from baseline (T0) to Month 6 and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2021
- Study start31 May 2021 (estimated)
- Primary completion31 Jul 2024 (estimated)
- Study completion31 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis RelapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roberto Bergamaschi, MD, Principal investigator, IRCCS Mondino Foundation, Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04902690
- Sponsor's protocol ID
- VEGF Study
- Status last verified
- May 2021
- First submitted
- 20 May 2021
- Last updated
- 26 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Amadio M, Bucolo C, Leggio GM, Drago F, Govoni S, Pascale A. The PKCbeta/HuR/VEGF pathway in diabetic retinopathy. Biochem Pharmacol. 2010 Oct 15;80(8):1230-7. doi: 10.1016/j.bcp.2010.06.033. Epub 2010 Jul 1.
PubMed 20599775Di Girolamo F, D'Amato A, Lante I, Signore F, Muraca M, Putignani L. Farm animal serum proteomics and impact on human health. Int J Mol Sci. 2014 Sep 1;15(9):15396-411. doi: 10.3390/ijms150915396.
PubMed 25257521Girolamo F, Coppola C, Ribatti D, Trojano M. Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol Commun. 2014 Jul 22;2:84. doi: 10.1186/s40478-014-0084-z.
PubMed 25047180Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.
PubMed 28002679Li R, Rezk A, Miyazaki Y, Hilgenberg E, Touil H, Shen P, Moore CS, Michel L, Althekair F, Rajasekharan S, Gommerman JL, Prat A, Fillatreau S, Bar-Or A; Canadian B cells in MS Team. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Sci Transl Med. 2015 Oct 21;7(310):310ra166. doi: 10.1126/scitranslmed.aab4176.
PubMed 26491076Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.
PubMed 28002688Moran EP, Wang Z, Chen J, Sapieha P, Smith LE, Ma JX. Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H738-49. doi: 10.1152/ajpheart.00005.2016. Epub 2016 Jul 29.
PubMed 27473938Pascale A, Govoni S. The complex world of post-transcriptional mechanisms: is their deregulation a common link for diseases? Focus on ELAV-like RNA-binding proteins. Cell Mol Life Sci. 2012 Feb;69(4):501-17. doi: 10.1007/s00018-011-0810-7. Epub 2011 Sep 10.
PubMed 21909784Riley JK, Sliwkowski MX. CD20: a gene in search of a function. Semin Oncol. 2000 Dec;27(6 Suppl 12):17-24.
PubMed 11225995Roscoe WA, Welsh ME, Carter DE, Karlik SJ. VEGF and angiogenesis in acute and chronic MOG((35-55)) peptide induced EAE. J Neuroimmunol. 2009 Apr 30;209(1-2):6-15. doi: 10.1016/j.jneuroim.2009.01.009. Epub 2009 Feb 23.
PubMed 19233483Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, Marta M, Leite I, Dubois B, Rubio J, Butzkueven H, Kilpatrick T, Mycko MP, Selmaj KW, Rio ME, Sa M, Salemi G, Savettieri G, Hillert J, Compston DA. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005 Apr 12;64(7):1144-51. doi: 10.1212/01.WNL.0000156155.19270.F8.
PubMed 15824338Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003 Oct 20;22(47):7359-68. doi: 10.1038/sj.onc.1206939.
PubMed 14576843Theoharides TC, Konstantinidou AD. Corticotropin-releasing hormone and the blood-brain-barrier. Front Biosci. 2007 Jan 1;12:1615-28. doi: 10.2741/2174.
PubMed 17127408
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observation Monocentric Study to Analyse the Possible Neuroprotective Effect of Ocrelizumab Via VEGF Protein Expression in Relapsing Multiple Sclerosis Patients
- ClinicalTrials.gov ID
- NCT04902690
- Acronym / sponsor ID
- VEGF Study
- Conditions
- Multiple Sclerosis Relapse
- Keywords
- Neuroprotective effect, Ocrelizumab, Multiple sclerosis, Vascular Endothelial Growth Factor
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" FoundationUniversity, hospital or other
- Study start
- 31 May 2021 (estimated)
- Primary completion
- 31 Jul 2024 (estimated)
- Study completion
- 31 Jul 2024 (estimated)
- First posted
- 26 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Ocrelizumab (OCR) is a humanized monoclonal anti-CD20 antibody approved by the FDA in 2017 and by the European Medicines Agency in 2018 for treatment of adult patients with Relapsing Multiple Sclerosis (RMS). In addition, having shown neuroprotective effects, OCR is the first drug ever approved for early treatment of Primary Progressive MS (PPMS). Currently, OCR is thought to mostly act via the rapid depletion of the B cells expressing CD20. Additionally, this depletion most likely causes long-lasting changes in the profile of B cells, characterized by a reduction of their pro-inflammatory phenotype, as demonstrated with other anti-CD20 antibodies.
Of interest, previous studies on other anti-CD20 drugs, mainly rituximab, have shown that anti-CD20 agents also exert interesting effects on additional intracellular signaling pathways, such as those involving serine/threonine and tyrosine kinases, as well as c-myc. Considering the structural, pharmacokinetic and pharmacodynamic similarities between OCR and rituximab, it can be hypothesized that the efficacy of OCR in delaying disease progression and neuroprotection might also stem from such intracellular effects.
Among the various intracellular effects elicited by rituximab through the binding with CD20, stimulation of the Protein Kinase C (PKC) pathway is of potential significance. The term PKC encompasses a family of several serine/threonine protein kinases of which the isoform β has been implicated in pathological processes, such as diabetic retinopathy, via a specific PKCβ/HuR/Vascular Endothelial Growth Factor (VEGF) pathway (Amadio et al. 2010). Notably, HuR belongs to a family of RNA-binding proteins, named ELAV, which are able to influence virtually any aspect of the post-synthesis fate of the targeted transcripts, including VEGF.
VEGF is a signaling molecule involved in vital processes such as angiogenesis, endothelial proliferation and cellular response to hypoxia. The possible role of VEGF in MS pathogenesis and evolution has not been explored until recently, but mounting evidence points to the conclusion that VEGF might play a significant noxious role in the relapsing stage of MS, for instance by mediating an increase in blood-brain barrier (BBB) permeability, while playing a beneficial, neuroprotective role in the late, progressive stage of the disease. Of note, VEGF has a primary role in promoting vascular hyperpermeability, indeed via phosphorylation of endothelial tight junction proteins modulates their degradation, finally leading to BBB disruption. Further, it also regulates vessel growth and is chemotactic for monocytes and lymphocytes, promoting neuroinflammation.
Of interest, a significant increase in VEGF was observed in mice in the acute phase of murine MOG-induced MS, which correlates to the clinical score, and in sera of MS patients during clinical disease relapses.
Based on these considerations, it can be possible that OCR exerts an additional beneficial effect in MS therapy by modulating VEGF content.
With this project, we aim to explore the effects of OCR on intracellular signaling pathways by assessing VEGF expression in Peripheral Blood Mononuclear Cells (PBMCs) of RMS patients at the beginning of OCR therapy, as well as at 6 and 12 months of ongoing treatment.
In particular, ther purpose of the study is to focus on the pro-angiogenic VEGF-A 165, which seems the isoform mainly involved as mediator of inflammation and cellular immunity.
Further, the PKCβ/HuR cascade will be investigated in the same conditions. Secondly, disease activity during OCR treatment will be examined at every step, and also compared with VEGF and PKC levels.
The results will also possibly demonstrate a necessity of further determining the extent and significance of intracellular effects of anti-CD20 therapy in MS.
This study is an observational (phase 4) , 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:
- Baseline/start (T0): informed consent signature, inclusion/exclusion criteria verification, demographical characteristics, clinical medical history recording, concomitant therapies, neurological history recording (MS history), number of relapses from MS onset, neurological examination, the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Severity Score (MSSS), blood sample, ocrelizumab administration.
- T6: (after 6 months of OCR treatment) adverse events (including relapses), neurological examination, therapies changes, EDSS, MSSS, blood sample, ocrelizumab administration.
- T12 (after 12 months* of OCR treatment), adverse events (including relapses), neurological examination, therapies changes, EDSS, MSSS, blood sample, ocrelizumab administration.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Age groups
- Adult
- Study population
- Patients with RMS, who are newly prescribed with OCR as per clinical practice, are enrolled.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
VEGF protein levels
Time frame: Month 12 versus baseline (T0)
To evaluate the expression of VEGF protein in PBMCs from patients with RMS
6 secondary outcomes
VEGF protein levels
Time frame: Month 6 versus baseline (T0)
VEGF mRNA levels
Time frame: Change from baseline (T0) to Month 6 and Month 12
PKCβ protein levels
Time frame: Change from baseline (T0) to Month 6 and Month 12
PKCβ mRNA levels
Time frame: Change from baseline (T0) to Month 6 and Month 12
Expanded Disability Status Scale (EDSS)
Time frame: Change from baseline (T0) to Month 6 and Month 12
Multiple Sclerosis Severity Score (MSSS)
Time frame: Change from baseline (T0) to Month 6 and Month 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2021.
- Background: PubMed 20599775Amadio M, Bucolo C, Leggio GM, Drago F, Govoni S, Pascale A. The PKCbeta/HuR/VEGF pathway in diabetic retinopathy. Biochem Pharmacol. 2010 Oct 15;80(8):1230-7. doi: 10.1016/j.bcp.2010.06.033. Epub 2010 Jul 1.
- Background: PubMed 25257521Di Girolamo F, D'Amato A, Lante I, Signore F, Muraca M, Putignani L. Farm animal serum proteomics and impact on human health. Int J Mol Sci. 2014 Sep 1;15(9):15396-411. doi: 10.3390/ijms150915396.
- Background: PubMed 25047180Girolamo F, Coppola C, Ribatti D, Trojano M. Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol Commun. 2014 Jul 22;2:84. doi: 10.1186/s40478-014-0084-z.
- Background: PubMed 28002679Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.
- Background: PubMed 26491076Li R, Rezk A, Miyazaki Y, Hilgenberg E, Touil H, Shen P, Moore CS, Michel L, Althekair F, Rajasekharan S, Gommerman JL, Prat A, Fillatreau S, Bar-Or A; Canadian B cells in MS Team. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Sci Transl Med. 2015 Oct 21;7(310):310ra166. doi: 10.1126/scitranslmed.aab4176.
- Background: PubMed 28002688Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.
- Background: PubMed 27473938Moran EP, Wang Z, Chen J, Sapieha P, Smith LE, Ma JX. Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H738-49. doi: 10.1152/ajpheart.00005.2016. Epub 2016 Jul 29.
- Background: PubMed 21909784Pascale A, Govoni S. The complex world of post-transcriptional mechanisms: is their deregulation a common link for diseases? Focus on ELAV-like RNA-binding proteins. Cell Mol Life Sci. 2012 Feb;69(4):501-17. doi: 10.1007/s00018-011-0810-7. Epub 2011 Sep 10.
- Background: PubMed 11225995Riley JK, Sliwkowski MX. CD20: a gene in search of a function. Semin Oncol. 2000 Dec;27(6 Suppl 12):17-24.
- Background: PubMed 19233483Roscoe WA, Welsh ME, Carter DE, Karlik SJ. VEGF and angiogenesis in acute and chronic MOG((35-55)) peptide induced EAE. J Neuroimmunol. 2009 Apr 30;209(1-2):6-15. doi: 10.1016/j.jneuroim.2009.01.009. Epub 2009 Feb 23.
- Background: PubMed 15824338Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, Marta M, Leite I, Dubois B, Rubio J, Butzkueven H, Kilpatrick T, Mycko MP, Selmaj KW, Rio ME, Sa M, Salemi G, Savettieri G, Hillert J, Compston DA. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005 Apr 12;64(7):1144-51. doi: 10.1212/01.WNL.0000156155.19270.F8.
- Background: PubMed 14576843Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003 Oct 20;22(47):7359-68. doi: 10.1038/sj.onc.1206939.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roberto Bergamaschi, MD principal investigator
IRCCS Mondino Foundation, Pavia
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis Relapse, run by IRCCS National Neurological Institute "C. Mondino" Foundation.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cinzia Fattore, MD (0382 380385, cinzia.fattore@mondino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VEGF protein levels (time frame: Month 12 versus baseline (T0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04902690, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2021.