Clinical trial NCT03217396: Biomarkers of Synaptic Damage in Multiple Sclerosis
Official title: Identification of New Biomarkers Useful to Define the Course of Multiple Sclerosis and Study of the Mechanisms That Promote Synaptic Damage
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Parkinson Disease
Amyotrophic Lateral Sclerosis
Alzheimer Disease
Keywords: synaptic plasticity
neuroinflammation
neurodegeneration
Lead sponsor: Neuromed IRCCS
Sponsor class: OTHER
Collaborators: name: IRCCS Multimedica
First posted: 2017-07-14
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: OTHER
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.

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.

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

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Identification of predictive biomarkers of SM using an ex vivo chimeric model
timeFrame: September 01 2020
Secondary outcomes:
measure: Identification of new therapeutic targets in MS.
timeFrame: September 01 2020
Other outcomes:
Locations:
city: Pozzilli
country: Italy
facility: IRCCS Neuromed
state: Isernia
Study officials:
affiliation: IRCCS Neuromed
name: Diego Centonze, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.