Biomarkers of Synaptic Damage in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Identification of New Biomarkers Useful to Define the Course of Multiple Sclerosis and Study of the Mechanisms That Promote Synaptic Damage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03217396
• Other study ID #: IRCCS Neuromed
• Status: Recruiting
• Start date: November 22, 2017
• Est. completion date: September 30, 2027

Study information

• Verified date: October 2022
• Source: Neuromed IRCCS
• Contact: Diego Centonze, MD
• Phone: +39 3934444159
• Email: centonze[@]uniroma2.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: September 30, 2027
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Multiple Sclerosis
• Parkinson Disease
• Sclerosis

Intervention

Procedure:
• lumbar puncture
lumbar puncture performed to detect OCB for diagnostic purposes

Locations

Country	Name	City	State
Italy	IRCCS Neuromed	Pozzilli	Isernia

Sponsors (2)

Lead Sponsor	Collaborator
Neuromed IRCCS	IRCCS Multimedica

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of predictive biomarkers of SM using an ex vivo chimeric model	CSF concentrations of: neurofilaments, beta amyloid, tau protein, inflammatory cytokines and microRNAs	September 01 2020
Secondary	Identification of new therapeutic targets in MS.	CSF concentrations of: neurofilaments, beta amyloid, tau protein, inflammatory cytokines and microRNAs	September 01 2020