Multiple Sclerosis: Chi3L1 and Treatment Efficacy

NCT04289675 | Completed

• 1 other identifier: CPRC 2018 / CHI3L1-MATHEY/MS
• Study Type: observational
• Target: 63
• Locations: 0 countries
• Sites: N/A

Brief Summary

Chitinase 3-like 1 (Chi3L1) is a Human protein synthetized by inflammatory cells. Its serum level increases in case of autoimmune diseases, and especially during multiple sclerosis (MS). There is a need for biological markers predictive of treatment efficacy. MS outcomes one year from treatment initiation are predictive of long-term treatment efficacy. The hypothesis is that serum Chi3L1 level before treatment initiation could predict one year MS outcomes. Primary objective: to show an association between the serum Chi3L1 level at diagnostic assessment and the clinical and radiological efficacy one year from initiation of the first disease modifying treatment (interferon beta, dimethyl fumarate or teriflunomide) in relapsing-onset multiple sclerosis (MS). Secondary objectives: to determine the threshold value of the serum Chi3L1 level predicting the efficacy of treatment, and the added value of other potential biomarkers in cerebrospinal fluid collected at diagnostic assessment: Chi3L1, light chains of neurofilaments and interleukin 6.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Statistical association between the baseline chitinase 3-like 1 serum level and being "responder" at year one

  Significant associations in each group of treatment Being "responder" means the presence of the four following : * No treatment withdrawal between months 3 and 15 after treatment initiation for reason of inefficacy * No relapse between months 3 and 15 * No increase of at least one point on the expanded disability status scale between months 3 and 15 * No gad-enhancing lesion on any magnetic resonance imaging scan between months 3 and 15 If any of these criteria is lacking, then the patient is considered as "non-responder".

  Baseline to month 15

Secondary Outcomes (4)

• Threshold chitinase 3-like 1 serum level at baseline to distinguish responders from non-responders

  Baseline to month 15

• Statistical association between the baseline chitinase 3-like 1 cerebrospinal fluid level and being "responder" at year one

  Baseline to month 15

• Statistical association between the baseline neurofilaments light chains cerebrospinal fluid level and being "responder" at year one

  Baseline to month 15

• Statistical association between the baseline interleukin 6 cerebrospinal fluid level and being "responder" at year one

  Baseline to month 15

Study Arms (3)

Interferon-Beta

Patients with first treatment : interferon beta (1a subcutaneous 22 or 44 µg thrice a week OR 1a intramuscular 30 µg once a week OR 1b subcutaneous 250 µg every other day OR 1a PEGylated subcutaneous 125 µg every two weeks)

Drug: Interferon-Beta

Dimethyl fumarate

Patients with first treatment : dimethyl fumarate (oral, 240 mg twice a day)

Teriflunomide

Patients with first treatment : teriflunomide (oral, 14 mg once a day)

Interventions

Interferon-Beta DRUG

Theses drugs have been administered as part of routine care. Biological samples that will be analyzed (blood and cerebrospinal fluid) have been taken as part of routine care.

Also known as: Dimethyl fumarate, Teriflunomide

Interferon-Beta

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients are selected from the Registre Lorrain des Scléroses en Plaques (ReLSEP). Demographical, clinical and paraclinical data are already collected in this database. Biological tests will be performed on their relative blood and cerebrospinal fluid samples, already taken and kept in the Centre de Ressources Biologiques Lorrain.

You may qualify if:

• Relapsing-onset multiple sclerosis according to the 2017 McDonald criteria
• Blood and cerebrospinal fluid samples collected at diagnostic assessment from 2012 January 1st and kept in the Centre de Ressources Biologiques Lorrain
• First platform disease modifying drugs : interferon-Beta, dimethyl fumarate or teriflunomide, introduced during the first 3 months after the diagnostic assessment
• Disease modifying drugs maintained at least 3 months
• Follow-up during at least 15 months after the first disease modifying drug initiation
• At least one brain magnetic resonance imaging with gadolinium injection between months 3 and 15 after disease modifying drug initiation

You may not qualify if:

• Objection to the use of personal data for research purpose

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples : chitinase 3-like 1 level Cerebrospinal fluid samples : chitinase 3-like 1, neurofilaments light chains and interleukin 6 levels

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Interferon-beta; Dimethyl Fumarate; teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Guillaume Mathey, MSc, MD

  Hôpital Central - service de Neurologie - CHRU Nancy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2019
• First Posted: February 28, 2020
• Study Start: January 1, 2012
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: March 9, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share