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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05088473
• Other study ID #: 21Neuro01
• Status: Completed
• Start date: October 15, 2021
• Est. completion date: October 31, 2021

Study information

• Verified date: November 2021
• Source: Centre Hospitalier Universitaire de Nice
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1500
• Est. completion date: October 31, 2021
• Est. primary completion date: October 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Central Nervous System Diseases
• Multiple Sclerosis
• Nervous System Diseases
• Sclerosis

Intervention

Other:
• Biological collection
Collection of cerebrospinal fluid kappa and lambda free light chains and indexes

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Clermont-Ferrand	Clermont-Ferrand
France	Centre Hospitalier Universitaire de Dijon	Dijon
France	Centre Hospitalier Universitaire de Grenoble	Grenoble
France	Centre Hospitalier Universitaire de Lille	Lille
France	Assistance Publique des Hôpitaux de Marseille	Marseille
France	Centre Hospitalier Universitaire de Montpellier	Montpellier
France	Centre Hospitalier Universitaire de Nantes	Nantes
France	Centre Hospitalier Universitaire de Nice	Nice
France	Centre Hospitalier Universitaire de Nîmes	Nîmes
France	Assistance Publique des Hôpitaux de Paris	Paris
France	Centre Hospitalier Universitaire de Saint-Etienne	Saint-Étienne
France	Centre Hospitalier Universitaire de Strasbourg	Strasbourg
France	Centre Hospitalier Universitaire de Toulouse	Toulouse
France	Centre Hospitalier Régional et Universaitaire de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nice

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of cerebrospinal fluid (CSF) and serum kappa and lambda free light chains (KFLC and LFLC)	Measurement of cerebrospinal fluid (CSF) and serum KFLC and LFLC by a turbilimetric analyzer (data in mg/L); Quantification of QKFLC and QLFLC (CSF FLC/serum FLC) in each group of patients; Compare median of QKFLC and QLFLC between groups	1 day
Primary	Measurement of cerebrospinal fluid (CSF) and serum albumin	Measurement of cerebrospinal fluid (CSF) and serum albumin by the same turbilimetric analyzer (data in mg/L); Quantification of albumin quotient (AQ) (CSF albumin/serum albumin) in each group of patients	1 day
Primary	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	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; 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; 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	1 day
Primary	Comparison of diagnostic performances of K/L FLC intrathecal synthesis biomarkers to oligoclonal bands (OCB) for multiple sclerosis	Identification of OCB status for each patient; Calculation of diagnostic performances of OCB (sensitivity, specificity and predictive values) for MS diagnostic; Comparison of diagnostic performances (sensitivity, specificity and predictive values) of OCB and K/L FLC intrathecal synthesis biomarkers for multiple sclerosis	1 day
Secondary	Evaluation of clinical data that can alter KFLC and LFLC values	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)	1 day