Biomarkers of Synaptic Damage in Multiple Sclerosis

Recruiting

• Conditions: Parkinson Disease; Amyotrophic Lateral Sclerosis; Multiple Sclerosis; Alzheimer Disease
• Interventions: Procedure: lumbar puncture

• Registration Number: NCT03217396
• Lead Sponsor: Neuromed IRCCS

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

Study Timeline

• Study First Submitted: 2017-07-12
• Study First Submitted QC: 2017-07-12
• Study First Posted: 2017-07-14
• Study Start: 2017-11-22
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-27
• Last Update Posted: 2022-10-28
• Primary Completion: 2026-09-01
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
control subjects	lumbar puncture	lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis
multiple sclerosis patients	lumbar puncture	lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis
neurodegenerative disease patients	lumbar puncture	lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

IRCCS Neuromed; 🇮🇹 Pozzilli, Isernia, Italy