Diagnosic and Pronostic Values of Kappa and Lambda Free Light Chains in Central Nervous System Inflammatory Diseases

Completed

• Conditions: Multiple Sclerosis; Central Nervous System Diseases
• Interventions: Other: Biological collection

• Registration Number: NCT05088473
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

Brief Summary

Numerous studies have shown the diagnostic interest of cerebrospinal fluid kappa free light chains and kappa index in multiple sclerosis. However, large cohort studies are lacking and little is known about the correlation between kappa and lambda indexes and multiple sclerosis evidence disease activity. Therefore, this study plan to validate the kappa and lambda free light chains and indexes as diagnostic biomarker in multiple sclerosis and to correlate the concentration of kappa and lambda free light chains with clinical and radiological activity in a large cohort of patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-13
• Study First Submitted QC: 2021-10-08
• Study Start: 2021-10-15
• Study First Posted: 2021-10-22
• Primary Completion: 2021-10-31
• Study Completion: 2021-10-31
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-08
• Last Update Posted: 2021-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

• Patients presenting with symptoms evocative of CNS involvement for who serum and cerebrospinal fluid kappa free light chains and kappa index are available

Exclusion Criteria

• Infectious CNS disease
• Tumor CNS disease
• Active CNS bleeding
• Monoclonal gammapathy
• Severe chronic renal failure (glomerular filtration rate <30 ml/mn)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CIS/RIS	Biological collection	-
Mutliple sclerosis	Biological collection	-
Non inflammatory CNS diseases	Biological collection	-
Other CNS inflammatory diseases	Biological collection	-

Primary Outcome Measures

Name	Time	Method
Measurement of cerebrospinal fluid (CSF) and serum kappa and lambda free light chains (KFLC and LFLC)	1 day	1. Measurement of cerebrospinal fluid (CSF) and serum KFLC and LFLC by a turbilimetric analyzer (data in mg/L); 2. Quantification of QKFLC and QLFLC (CSF FLC/serum FLC) in each group of patients; 3. Compare median of QKFLC and QLFLC between groups
Measurement of cerebrospinal fluid (CSF) and serum albumin	1 day	1. Measurement of cerebrospinal fluid (CSF) and serum albumin by the same turbilimetric analyzer (data in mg/L); 2. Quantification of albumin quotient (AQ) (CSF albumin/serum albumin) in each group of patients
Evaluation of the diagnostic performances of KFLC and LFLC intrathecal synthesis biomarkers (K/L FLC index and K/L FLC intrathecal fraction (IF)) for multiple sclerosis	1 day	1. Calculation of KFLC intrathecal synthesis biomarkers: KFLC index = (CSF KFLC/serum KFLC) / AQ; KFLC IF = (KFLC(loc)/CSF KFLC) x 100 with: KFLC(loc) = ((CSF KFLC/serum KFLC) / Qk(lim)) x serum KFLC and Qk(lim) = 3.27 x (AQ\^2 + 33)\^0.5 - 8.2; 2. Calculation of LFLC intrathecal synthesis biomarkers: LFLC index = (CSF LFLC/serum LFLC) / AQ); LFLC IF = (LFLC(loc)/CSF LFLC) x 100 with: LFLC(loc) = ((CSF LFLC/serum LFLC) / Ql(lim)) x serum LFLC and Ql(lim) = 2.1138 x AQ\^0.865; 3. Determination of diagnostic performances by ROC curve analysis and best cut-off values with the Younden index to calculate sensitivity, specificity and predictive values for MS diagnosis
Comparison of diagnostic performances of K/L FLC intrathecal synthesis biomarkers to oligoclonal bands (OCB) for multiple sclerosis	1 day	1. Identification of OCB status for each patient; 2. Calculation of diagnostic performances of OCB (sensitivity, specificity and predictive values) for MS diagnostic; 3. Comparison of diagnostic performances (sensitivity, specificity and predictive values) of OCB and K/L FLC intrathecal synthesis biomarkers for multiple sclerosis

Secondary Outcome Measures

Name	Time	Method
Evaluation of clinical data that can alter KFLC and LFLC values	1 day	Identification of data that can be independtly associated with high or low CSF KFLC or LFLC values as potential bias in K/L FLC intrathecal synthesis biomarkers interpretation: * Gender; * Age; * Type of clinical demyelinating event (i.e. myelitis, optic neuritis...); * Immune modifying drug treatment ongoing during sampling; * Underlying disease activity (measured by the presence of subacute clinical symptoms ongoing at sampling or gadolinium enhanced lesions within the last MRI status)

Trial Locations

Locations (14)

Centre Hospitalier Universitaire de Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

Centre Hospitalier Universitaire de Nantes; 🇫🇷 Nantes, France

Centre Hospitalier Universitaire de Nice; 🇫🇷 Nice, France

Assistance Publique des Hôpitaux de Paris; 🇫🇷 Paris, France

Centre Hospitalier Universitaire de Nîmes; 🇫🇷 Nîmes, France

Centre Hospitalier Régional et Universaitaire de Tours; 🇫🇷 Tours, France

Centre Hospitalier Universitaire de Saint-Etienne; 🇫🇷 Saint-Étienne, France

Centre Hospitalier Universitaire de Strasbourg; 🇫🇷 Strasbourg, France

Centre Hospitalier Universitaire de Montpellier; 🇫🇷 Montpellier, France

Centre Hospitalier Universitaire de Dijon; 🇫🇷 Dijon, France

Centre Hospitalier Universitaire de Lille; 🇫🇷 Lille, France

Centre Hospitalier Universitaire de Grenoble; 🇫🇷 Grenoble, France

Assistance Publique des Hôpitaux de Marseille; 🇫🇷 Marseille, France

Centre Hospitalier Universitaire de Toulouse; 🇫🇷 Toulouse, France