Multiple Sclerosis: Chi3L1 and Treatment Efficacy

Chi3L1: A Marker of Efficacy of Platform Treatments in Relapsing-onset Multiple Sclerosis: A Prognostic Study on Existing Clinical Data and Biological Samples

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Interferon-Beta

• Study Type: Observational
• Enrollment (Actual): 63

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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.; Other Names: Dimethyl fumarate; Teriflunomide
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Threshold chitinase 3-like 1 serum level at baseline to distinguish responders from non-responders	Threshold measure that discriminates responders and non-responders at month 15 in each group	Baseline to month 15
Statistical association between the baseline chitinase 3-like 1 cerebrospinal fluid 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
Statistical association between the baseline neurofilaments light chains cerebrospinal fluid 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
Statistical association between the baseline interleukin 6 cerebrospinal fluid 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

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Guillaume Mathey, MSc, MD, Hôpital Central - service de Neurologie - CHRU Nancy

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2012
• Primary Completion (ACTUAL): December 1, 2019
• Study Completion (ACTUAL): December 1, 2019

Study Registration Dates

• First Submitted: December 27, 2019
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (ACTUAL): February 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2020
• Last Update Submitted That Met QC Criteria: March 5, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Interferons; Interferon-beta; Dimethyl Fumarate; Teriflunomide
• Other Study ID Numbers: CPRC 2018 / CHI3L1-MATHEY/MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No