Multiple SclerosisPRO-KFLCNCT07183020
Kappa Free Light Chains (KFLC) in Multiple Sclerosis (MS) and Clinically Isolated Syndrome (CIS)
An observational study of Multiple Sclerosis and Clinically Isolated Syndrome (CIS), run by Skripuletz, Thomas Prof. Dr. at 1 site in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis, Clinically Isolated Syndrome (CIS)
- What is being tested?
- Oligoclonal bands and kappa free light chains (KFLC)
- How many people
- 1,142 participants
- Where
- 1 siteGermany
- Study dates
- 27 Oct 2022to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- no diagnosis of MS or CIS according to 2017-revised McDonald criteria for MS
- no available cerebrospinal fluid (CSF) and serum sample pairs
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site
Medizinische Hochschule Hannover / Hannover Medical School
Hanover, Lower Saxony, 30625
About this study
Official title: Prospective, Multicentric, Real-world Investigation of Kappa Free Light Chains (KFLC) in Multiple Sclerosis (MS) and Clinically Isolated Syndrome (CIS)
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.
Read the detailed description
In this multicenter study, paired cerebrospinal fluid (CSF) and serum samples from patients with chronic inflammatory diseases of the central nervous system (multiple sclerosis (MS) / clinically isolated syndrome (CIS)) are investigated to evaluate the diagnostic utility of CSF-specific oligoclonal bands and kappa free light chains (KFLC). Both biomarkers have already demonstrated diagnostic relevance in this patient population, but comparative multicenter studies are still lacking. Another key challenge for the clinical implementation of KFLC is the absence of standardized reference values, as different cut-offs were proposed.
To address this gap, CSF-specific oligoclonal bands and KFLC are prospectively analyzed in a multicenter cohort of patients with MS / CIS. Samples and associated data are collected prospectively and partially retrospectively from participating centers. Included patients are followed longitudinally to determine whether conversion from CIS to clinical definite MS occurs and to monitor disease progression over time.
- Being tested
- Oligoclonal bands and kappa free light chains (KFLC)
- Keywords
- multiple sclerosis, clinically isolated syndrome, cerebrospinal fluid, kappa free light chains, oligoclonal bands, biomarker, diagnosis
- Medical subject headings
- Multiple Sclerosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Diagnostic Test: Oligoclonal bands and kappa free light chains (KFLC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
The frequence of an intrathecal kappa free light chains (KFLC) synthesis as assessed by Reiber´s diagram is significantly higher as compared to the KFLC index of 6.1 as cut-off
Measured: From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2025
- Study start27 Oct 2022
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,142 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Skripuletz, Thomas Prof. Dr.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Skripuletz, Thomas Prof. Dr., Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07183020
- Sponsor's protocol ID
- 10167_B0_K2022
- Acronym
- PRO-KFLC
- Status last verified
- Jul 2025
- First submitted
- 10 Sep 2025
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pseudonym, immunoglobulin (Ig) G serum (g/l), IgG cerebrospinal fluid (CSF) (mg/l), Q IgG, Albumin serum (g/l), Albumin CSF (mg/l), Q-Albumin
Publications
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.
PubMed 30501024Schwenkenbecher 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.
PubMed 31744096Konen 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.
PubMed 32244362Konen 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.
PubMed 34831279Susse 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.
PubMed 35328273Konen 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.
PubMed 35448006Konen 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.
PubMed 35884934Hannich 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.
PubMed 39039726Konen 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.
PubMed 39947571
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Multicentric, Real-world Investigation of Kappa Free Light Chains (KFLC) in Multiple Sclerosis (MS) and Clinically Isolated Syndrome (CIS)
- ClinicalTrials.gov ID
- NCT07183020
- Acronym / sponsor ID
- PRO-KFLC / 10167_B0_K2022
- Keywords
- multiple sclerosis, clinically isolated syndrome, cerebrospinal fluid, kappa free light chains, oligoclonal bands, biomarker, diagnosis
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 1,142 participants (estimated)
- Lead sponsor
- Skripuletz, Thomas Prof. Dr.University, hospital or other
- Study start
- 27 Oct 2022 (actual)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 19 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this multicenter study, paired cerebrospinal fluid (CSF) and serum samples from patients with chronic inflammatory diseases of the central nervous system (multiple sclerosis (MS) / clinically isolated syndrome (CIS)) are investigated to evaluate the diagnostic utility of CSF-specific oligoclonal bands and kappa free light chains (KFLC). Both biomarkers have already demonstrated diagnostic relevance in this patient population, but comparative multicenter studies are still lacking. Another key challenge for the clinical implementation of KFLC is the absence of standardized reference values, as different cut-offs were proposed.
To address this gap, CSF-specific oligoclonal bands and KFLC are prospectively analyzed in a multicenter cohort of patients with MS / CIS. Samples and associated data are collected prospectively and partially retrospectively from participating centers. Included patients are followed longitudinally to determine whether conversion from CIS to clinical definite MS occurs and to monitor disease progression over time.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multiple sclerosis (MS) / clinically isolated syndrome (CIS) | – | Diagnostic Test: Oligoclonal bands and kappa free light chains (KFLC)Patients diagnosed with multiple sclerosis (MS) or clinically isolated syndrome (CIS) and an available pair of cerebrospinal fluid (CSF) and serum |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (2 listed)
- no diagnosis of MS or CIS according to 2017-revised McDonald criteria for MS
- no available cerebrospinal fluid (CSF) and serum sample pairs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oligoclonal bands and kappa free light chains (KFLC)Comparison of oligoclonal bands and kappa free light chains (KFLC) in patients with multiple sclerosis (MS) / clinically isolated syndrome (CIS) | Diagnostic test | Multiple sclerosis (MS) / clinically isolated syndrome (CIS) |
Primary outcome
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
Time frame: From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months
Evidence of an intrathecal kappa free light chains (KFLC) synthesis is equally sensitive to assess for an intrathecal immunglobulin synthesis compared with oligoclonal bands
1 secondary outcome
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
Time frame: From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Background: PubMed 30501024Schwenkenbecher 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.
- Background: PubMed 31744096Schwenkenbecher 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.
- Background: PubMed 32244362Konen 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.
- Background: PubMed 34831279Konen 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.
- Background: PubMed 35328273Susse 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.
- Background: PubMed 35448006Konen 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.
- Background: PubMed 35884934Konen 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.
- Background: PubMed 39039726Hannich 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.
- Background: PubMed 39947571Konen 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.
- Individual participant dataSharing planned: Yes. Pseudonym, immunoglobulin (Ig) G serum (g/l), IgG cerebrospinal fluid (CSF) (mg/l), Q IgG, Albumin serum (g/l), Albumin CSF (mg/l), Q-Albumin
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis and Clinically Isolated Syndrome (CIS), run by Skripuletz, Thomas Prof. Dr. at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07183020, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.