Neurofilament Light Chain in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

— NfL-ALS  

Official title:

Performance of Serum Neurofilament Light Chain in a Wide Spectrum of Clinical Courses of Amyotrophic Lateral Sclerosis - a Cross-sectional and Longitudinal Multicenter Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06201650
• Other study ID #: NfL-ALS
• Status: Recruiting
• Start date: November 11, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: Charite University, Berlin, Germany
• Contact: Thomas Meyer, MD
• Phone: 004930450560028
• Email: thomas.meyer[@]charite.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study assesses the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of ALS progression, disease duration, and tracheostomy invasive ventilation (TIV). The aim of the research project is to investigate the correlation between NfL serum concentration and the natural course of the disease, the ALS progression rate, and specific phenotypes of ALS. Furthermore, the performance of NfL as a therapeutic biomarker will be studied. A systematic analysis of the NfL serum concentration in a cohort of 3,000 ALS patients using the Single Molecule Analysis method (SIMOA) will be performed. This analysis is carried out as a multi-center study.

Description:

The aim of this study is to investigate the correlation between the NfL serum concentration and the natural course of the disease, the ALS progression rate as measured by the ALS functional rating scale (ALSFRS-R), and specific phenotypes of ALS. The results of the study will contribute to the assessment of disease progression and the prognosis making of ALS. Furthermore, the performance of NfL as a therapeutic marker of ALS medicines and non-pharmacologic treatment options will be investigated. A systematic analysis of the NfL serum concentration in an extended cohort of ALS patients using the Single Molecule Analysis method (SIMOA) will be performed.

Research objectives comprise:

• Correlation of NfL with disease progression, including duration of ALS disease

• Correlation of NfL with the course of ALS (classic ALS or variants in the motor neuron involvement or the regional propagation patterns)

• Correlation of NfL with the progression rate of ALS

Cohorts on phenotypic variants:

The clinical phenotype of ALS will be differentiated according to the motor neuron involvement or regional propagation patterns of disease onset and clinical course.

ALS variants in relation to motor neuron involvement:

• Typical ALS: clinical features for an affection of the 1st and 2nd motor neurons are present

• Progressive muscular atrophy (PMA): only clinical features for an affection of the 2nd motor neuron are present

• Spastic ALS: predominantly clinical features for an affection of the 1st motor neuron and fewer signs of an affection of the 2nd motor neuron

• Primary lateral sclerosis (PLS): only clinical features for an affection of the 1st motor neuron are present

ALS variants in regional propagation patterns:

• Typical form: paresis of the upper or lower extremities or the bulbar region as well as the spread of the paresis to other regions

• Flail arm syndrome: primary and dominant paresis of the upper extremities and little or delayed spread of the paresis to other regions

• Flail leg syndrome: primary and dominant paresis of the lower extremities and little or delayed spread of the paresis to other regions

• Axial ALS: primary and dominant paresis of the trunk muscles and minor or delayed spread of the paresis to other regions

• Progressive bulbar paralysis: primary and dominant paresis in the bulbar region and slight or delayed spread of the paresis to other regions

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3000
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of amyotrophic lateral sclerosis including specific forms

• Patient's informed consent to participate in this study

• Minimum age of 18 years

• Willingness for blood collection

Exclusion Criteria:

• Unwillingness to store and share pseudonymized medical data collected in the study

• Evaluation by the investigator, which excludes participation

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Diagnostic Test:
• Neurofilament light chain
Neurofilament light chain as biomarker for amyotrophic lateral sclerosis

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Vivantes Klinikum Kaulsdorf	Berlin
Germany	Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH	Bochum
Germany	Universitätsklinikum Bonn	Bonn
Germany	Technische Universität Dresden	Dresden
Germany	Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH	Essen
Germany	Universitätsklinikum Essen	Essen
Germany	Georg-August-Universität Göttingen Universitätsmedizin Göttingen	Göttingen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Jena	Jena
Germany	Universität Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Universität Heidelberg Medizinische Fakultät Mannheim	Mannheim
Germany	Klinikum rechts der Isar der Technischen Universität München	München
Germany	Westfälische Wilhelms-Universität Münster	Münster
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsmedizin Rostock	Rostock
Germany	Universitätsklinikum Ulm	Ulm

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Boris Canessa ALS Stiftung

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	correlation of serum neurofilament light chain to ALS progression	correlation of serum neurofilament light chain (NfL) with the ALS progression rate as measured by the revised form of the ALS function rating scale (ALSFRS-R)	2020-2024
Primary	correlation of serum neurofilament light chain with ALS phenotypes	correlation of serum neurofilament light chain with ALS phenotypes in terms of type of onset and clinical variants including progressive muscle atrophy, primary lateral sclerosis, flail-arm syndrome, flail-leg syndrome and other phenotypes	2020-2024
Primary	correlation of serum neurofilament light chain with ALS treatment options	correlation of serum neurofilament light chain to ALS interventions such as treatment with tofersen and other medicines	2020-2024
Secondary	correlation of serum neurofilament light chain with non-pharmacologic ALS interventions	correlation of serum neurofilament light chain with non-pharmacologic ALS interventions including nutrition or ventilation treatment	2022-2024

External Links

•   Website of funding organization
•   Website of principle investigator