Biomarkers of Synaptic Damage in Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT03217396

Recruitment Status : Recruiting

First Posted : July 14, 2017

Last Update Posted : October 28, 2022

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

IRCCS Multimedica

Information provided by (Responsible Party):

Mario Stampanoni Bassi, Neuromed IRCCS

Study Description

Brief Summary:

A prospective and retrospective cohort study of about five years will be performed on blood and cerebrospinal fluid samples taken for diagnostic reasons from recruited patients within the Neuromed Neurology Unit. Subjects with other chronic neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD), and healthy subjects subjected to blood sampling and / or lumbar puncture for clinical reasons will be recruited As control groups.

Condition or disease	Intervention/treatment
Multiple Sclerosis Parkinson Disease Amyotrophic Lateral Sclerosis Alzheimer Disease	Procedure: lumbar puncture

Detailed Description:

Blood and cerebrospinal fluid samples will be subjected to the procedures required for the isolation of the different components immediately after the withdrawal. Subsequently, the levels of microRNAs, cytokines, chemokines, cell growth factors, neuronal damage markers (tau, phosphorylated and truncated tau, neurofilaments) and mitochondrial (lactate) and free d-amino acids (Objective 1) will be determined. Furthermore, synaptic alterations will be evaluated in the ex vivo chimeric model of MS, using the patch-clamp technique (Objective 2). Genotyping studies will be conducted in order to identify single nucleotide polymorphisms (SNPs) in coding and / or regulating regions of genes (microRNAs or proteins) involved in alterations of the synaptic transmission of MS and its murine experimental model (i.e. SLC1A3, NGFB, PDGFA, etc.), which correlate with specific clinical parameters (i.e. EDSS, BREMS, disease progression index, MS type, disease activity, etc.) and with the levels of potential biomarkers identified

Study Design

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Study Type :	Observational
Estimated Enrollment :	300 participants
Observational Model:	Case-Control
Time Perspective:	Other
Official Title:	Identification of New Biomarkers Useful to Define the Course of Multiple Sclerosis and Study of the Mechanisms That Promote Synaptic Damage
Actual Study Start Date :	November 22, 2017
Estimated Primary Completion Date :	September 1, 2026
Estimated Study Completion Date :	September 30, 2027

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Alzheimer disease Amyotrophic lateral sclerosis Multiple sclerosis Parkinson disease Juvenile primary lateral sclerosis

MedlinePlus related topics: Multiple Sclerosis

Genetic and Rare Diseases Information Center resources: Familial Alzheimer Disease Primary Lateral Sclerosis Amyotrophic Lateral Sclerosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
multiple sclerosis patients lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis	Procedure: lumbar puncture lumbar puncture performed to detect OCB for diagnostic purposes
neurodegenerative disease patients lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis	Procedure: lumbar puncture lumbar puncture performed to detect OCB for diagnostic purposes
control subjects lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis	Procedure: lumbar puncture lumbar puncture performed to detect OCB for diagnostic purposes

Outcome Measures

Primary Outcome Measures :

Identification of predictive biomarkers of SM using an ex vivo chimeric model [ Time Frame: September 01 2020 ]
CSF concentrations of: neurofilaments, beta amyloid, tau protein, inflammatory cytokines and microRNAs

Secondary Outcome Measures :

Identification of new therapeutic targets in MS. [ Time Frame: September 01 2020 ]
CSF concentrations of: neurofilaments, beta amyloid, tau protein, inflammatory cytokines and microRNAs

Biospecimen Retention: Samples With DNA

blood samples

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

patients recruited within the Neurology Unit, IRCCS Neuromed. Subjects with other chronic neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD), and healthy subjects subjected to blood sampling and / or lumbar puncture for clinical reasons will be recruited as control group.

Criteria

Inclusion Criteria:

Male and female patients (age between 18 and 65 years)
Diagnosis of MS in accordance with McDonald's (2010 rev) criteria,
EDSS between 0 and 5.5 (included),
Patients able to provide informed consent to participation in the study

Exclusion Criteria:

Inability to provide informed written consent
Altered basal blood count
Pregnancy or lactation
Contraindications for the execution of magnetic resonance imaging with gadolinium
Significant clinical conditions in addition to SM or other chronic neurodegenerative diseases including latent viral infections

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03217396

Contacts

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Contact: Diego Centonze, MD	+39 3934444159	centonze@uniroma2.it
Contact: Mario Stampanoni Bassi, MD	+39 3460181370	mario_sb@hotmail.it

Locations

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Italy
IRCCS Neuromed	Recruiting
Pozzilli, Isernia, Italy, 86077
Contact: Stefania Passarelli +39 0865.915217 direzionescientifica@neuromed.it

Sponsors and Collaborators

Neuromed IRCCS

IRCCS Multimedica

Investigators

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Principal Investigator:	Diego Centonze, MD	IRCCS Neuromed

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mandolesi G, Rizzo FR, Balletta S, Stampanoni Bassi M, Gilio L, Guadalupi L, Nencini M, Moscatelli A, Ryan CP, Licursi V, Dolcetti E, Musella A, Gentile A, Fresegna D, Bullitta S, Caioli S, Vanni V, Sanna K, Bruno A, Buttari F, Castelli C, Presutti C, De Santa F, Finardi A, Furlan R, Centonze D, De Vito F. The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis. Cells. 2021 Feb 5;10(2):330. doi: 10.3390/cells10020330.

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Responsible Party:	Mario Stampanoni Bassi, Principal Investigator, Neuromed IRCCS
ClinicalTrials.gov Identifier:	NCT03217396
Other Study ID Numbers:	IRCCS Neuromed
First Posted:	July 14, 2017 Key Record Dates
Last Update Posted:	October 28, 2022
Last Verified:	October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Mario Stampanoni Bassi, Neuromed IRCCS:


synaptic plasticity neuroinflammation neurodegeneration

Additional relevant MeSH terms:

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Parkinson Disease Multiple Sclerosis Alzheimer Disease Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes 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 Dementia Tauopathies Neurocognitive Disorders Mental Disorders Neuromuscular Diseases Spinal Cord Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases

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