Multiple Sclerosis: Chi3L1 and Treatment Efficacy

Completed

• Conditions: Multiple Sclerosis
• Interventions: Drug: Interferon-Beta

• Registration Number: NCT04289675
• Lead Sponsor: Central Hospital, Nancy, France

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-01
• Status Verified: 2019-12
• Primary Completion: 2019-12-01
• Study Completion: 2019-12-01
• Study First Submitted: 2019-12-27
• Study First Submitted QC: 2020-02-27
• Study First Posted: 2020-02-28
• Last Update Submitted: 2020-03-05
• Last Update Posted: 2020-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

• 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

Exclusion Criteria

• Objection to the use of personal data for research purpose

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Interferon-Beta	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)

Primary Outcome Measures

Name	Time	Method
Statistical association between the baseline chitinase 3-like 1 serum level and being "responder" at year one	Baseline to month 15	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".

Secondary Outcome Measures

Name	Time	Method
Threshold chitinase 3-like 1 serum level at baseline to distinguish responders from non-responders	Baseline to month 15	Threshold measure that discriminates responders and non-responders at month 15 in each group
Statistical association between the baseline chitinase 3-like 1 cerebrospinal fluid level and being "responder" at year one	Baseline to month 15	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".
Statistical association between the baseline neurofilaments light chains cerebrospinal fluid level and being "responder" at year one	Baseline to month 15	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".
Statistical association between the baseline interleukin 6 cerebrospinal fluid level and being "responder" at year one	Baseline to month 15	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".