Kappa Free Light Chains (KFLC) in Multiple Sclerosis (MS) and Clinically Isolated Syndrome (CIS)

NCT07183020 | Enrolling By Invitation

• 1 other identifier: 10167_B0_K2022
• Study Type: observational
• Target: 1,142
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn about the role of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) in the diagnosis of multiple sclerosis (MS) and clinically isolated syndrome (CIS). The main question it aims to answer is: Are KFLC superior, inferior or equally useful in the diagnostic work-up of CSF of patients with MS and CIS? In CSF and serum sample pairs of patients diagnosed with MS or CIS, KFLC are measured using a nephelometric assay and are compared with the gold standard, of CSF diagnostics, oligoclonal bands.

Conditions

Multiple Sclerosis; Clinically Isolated Syndrome (CIS)

Keywords

multiple sclerosis; clinically isolated syndrome; cerebrospinal fluid; kappa free light chains; oligoclonal bands; biomarker; diagnosis

Outcome Measures

Primary Outcomes (1)

• Non-inferiority of diagnostic sensitivity of cerebrospinal fluid (CSF) kappa free light chains (KFLC) in multiple sclerosis (MS) and clinically isolated syndrome (CIS) compared to oligoclonal bands

  Evidence of an intrathecal kappa free light chains (KFLC) synthesis is equally sensitive to assess for an intrathecal immunglobulin synthesis compared with oligoclonal bands

  From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months

Secondary Outcomes (1)

• Superiority of Reiber´s diagram for kappa free light chains (KFLC) compared to KFLC index of 6.1 to assess for an intrathecal KFLC synthesis in multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients

  From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months

Study Arms (1)

Multiple sclerosis (MS) / clinically isolated syndrome (CIS)

Patients diagnosed with multiple sclerosis (MS) or clinically isolated syndrome (CIS) and an available pair of cerebrospinal fluid (CSF) and serum

Diagnostic Test: Oligoclonal bands and kappa free light chains (KFLC)

Interventions

Oligoclonal bands and kappa free light chains (KFLC) DIAGNOSTIC_TEST

Comparison of oligoclonal bands and kappa free light chains (KFLC) in patients with multiple sclerosis (MS) / clinically isolated syndrome (CIS)

Multiple sclerosis (MS) / clinically isolated syndrome (CIS)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients being adult, diagnosed with multiple sclerosis (MS) or clinically isolated syndrome (CIS), receiving a cerebrospinal fluid (CSF) analysis as part of the clinical routine diagnostic work-up

You may qualify if:

• patients diagnosed with multiple sclerosis (MS) or clinically isolated syndrome (CIS) according to 2017-revised McDonald criteria for MS
• age between 18 and 70 years

You may not qualify if:

• no diagnosis of MS or CIS according to 2017-revised McDonald criteria for MS
• no available cerebrospinal fluid (CSF) and serum sample pairs

Sponsors & Collaborators

• Skripuletz, Thomas Prof. Dr.: lead

Study Sites (1)

Medizinische Hochschule Hannover / Hannover Medical School

Hanover, Lower Saxony, 30625, Germany

Location

Related Publications (9)

• Schwenkenbecher P, Konen FF, Wurster U, Jendretzky KF, Gingele S, Suhs KW, Pul R, Witte T, Stangel M, Skripuletz T. The Persisting Significance of Oligoclonal Bands in the Dawning Era of Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis. Int J Mol Sci. 2018 Nov 29;19(12):3796. doi: 10.3390/ijms19123796.

  PMID: 30501024 BACKGROUND

• Schwenkenbecher P, Konen FF, Wurster U, Witte T, Gingele S, Suhs KW, Stangel M, Skripuletz T. Reiber's Diagram for Kappa Free Light Chains: The New Standard for Assessing Intrathecal Synthesis? Diagnostics (Basel). 2019 Nov 16;9(4):194. doi: 10.3390/diagnostics9040194.

  PMID: 31744096 BACKGROUND

• Konen FF, Wurster U, Witte T, Jendretzky KF, Gingele S, Tumani H, Suhs KW, Stangel M, Schwenkenbecher P, Skripuletz T. The Impact of Immunomodulatory Treatment on Kappa Free Light Chains as Biomarker in Neuroinflammation. Cells. 2020 Mar 31;9(4):842. doi: 10.3390/cells9040842.

  PMID: 32244362 BACKGROUND

• Konen FF, Schwenkenbecher P, Jendretzky KF, Gingele S, Suhs KW, Tumani H, Susse M, Skripuletz T. The Increasing Role of Kappa Free Light Chains in the Diagnosis of Multiple Sclerosis. Cells. 2021 Nov 6;10(11):3056. doi: 10.3390/cells10113056.

  PMID: 34831279 BACKGROUND

• Susse M, Konen FF, Schwenkenbecher P, Budde K, Nauck M, Grothe M, Hannich MJ, Skripuletz T. Decreased Intrathecal Concentrations of Free Light Chains Kappa in Multiple Sclerosis Patients Taking Very High Effective Disease-Modifying Treatment. Diagnostics (Basel). 2022 Mar 16;12(3):720. doi: 10.3390/diagnostics12030720.

  PMID: 35328273 BACKGROUND

• Konen FF, Schwenkenbecher P, Jendretzky KF, Gingele S, Witte T, Suhs KW, Grothe M, Hannich MJ, Susse M, Skripuletz T. Kappa Free Light Chains in Cerebrospinal Fluid in Inflammatory and Non-Inflammatory Neurological Diseases. Brain Sci. 2022 Apr 3;12(4):475. doi: 10.3390/brainsci12040475.

  PMID: 35448006 BACKGROUND

• Konen FF, Hannich MJ, Schwenkenbecher P, Grothe M, Gag K, Jendretzky KF, Gingele S, Suhs KW, Witte T, Skripuletz T, Susse M. Diagnostic Cerebrospinal Fluid Biomarker in Early and Late Onset Multiple Sclerosis. Biomedicines. 2022 Jul 7;10(7):1629. doi: 10.3390/biomedicines10071629.

  PMID: 35884934 BACKGROUND

• Hannich MJ, Konen FF, Gag K, Alkhayer A, Turker SN, Budde K, Nauck M, Wurster U, Dressel A, Skripuletz T, Susse M. Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid. Clin Chem Lab Med. 2024 Jul 23;63(1):147-153. doi: 10.1515/cclm-2023-1468. Print 2025 Jan 29.

  PMID: 39039726 BACKGROUND

• Konen FF, Wurster U, Schwenkenbecher P, Gerritzen A, Gross CC, Eichhorn P, Harrer A, Isenmann S, Lewczuk P, Lewerenz J, Leypoldt F, Otto M, Regeniter A, Roskos M, Ruprecht K, Spreer A, Strik H, Uhr M, Wick M, Wildemann B, Wiltfang J, Zimmermann T, Hannich M, Khalil M, Tumani H, Susse M, Skripuletz T; German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurochemistry (DGLN e.V.). Oligoclonal bands and kappa free light chains: Competing parameters or complementary biomarkers? Autoimmun Rev. 2025 Apr 30;24(5):103765. doi: 10.1016/j.autrev.2025.103765. Epub 2025 Feb 11.

  PMID: 39947571 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Paired samples of serum and cerebrospinal fluid

MeSH Terms

Conditions

Multiple Sclerosis; Disease

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med., MD

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 19, 2025
• Study Start: October 27, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: 27.10.2022 beginning ending 10 years after publication
• Access Criteria: Individual participant data (IPD) will be stored and processed in pseudonymized form on the server of the computing center of Hannover Medical School (MHH) in compliance with data protection regulations, in particular the EU General Data Protection Regulation (GDPR). Access to the pseudonymized data and their processing will be restricted to authorized study team members who are bound by confidentiality obligations. Unused data will be deleted. Remaining data will be archived for ten years after study completion in accordance with good scientific practice guidelines and will be irreversibly deleted thereafter. No external parties will have access to the IPD or supporting information.

Locations

DE (1)