Neurofilament Light Chain in Amyotrophic Lateral Sclerosis (NfL-ALS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Diagnostic test: Neurofilament light chain

Detailed 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

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: Thomas Meyer, MD; Phone Number: 004930450560028; Email: thomas.meyer@charite.de
• Study Contact Backup: Name: Péter Körtvélyessy, MD; Phone Number: 004930450560028; Email: peter.koertvelyessy@charite.de

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Not yet recruiting
    • Medizinische Universität Innsbruck
    • Contact: Wolfgang Löscher, Prof Dr
    • Principal Investigator: Wolfgang Löscher, Prof Dr
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité Universitätsmedizin Berlin
    • Contact: Thomas Meyer, Prof Dr; Email: thomas.meyer@charite.de
    • Contact: Erma Salkic; Email: erma.salkic@charite.de
    • Principal Investigator: Thomas Meyer, Prof Dr
  • Berlin, Germany, 12621
    • Recruiting
    • Vivantes Klinikum Kaulsdorf
    • Contact: Christoph Richter, Dr
    • Principal Investigator: Christoph Richter, Dr
  • Bochum, Germany, 44789
    • Recruiting
    • Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH
    • Contact: Ute Weyen, Dr
    • Principal Investigator: Ute Weyen, Dr
  • Bonn, Germany, 53127
    • Recruiting
    • Universitätsklinikum Bonn
    • Contact: Patrick Weydt, PD Dr
    • Principal Investigator: Patrick Weydt, PD Dr
  • Dresden, Germany, 01062
    • Recruiting
    • Technische Universitat Dresden
    • Contact: René Günther, Dr
    • Principal Investigator: René Günther, Dr
  • Essen, Germany, 45147
    • Recruiting
    • Universitätsklinikum Essen
    • Contact: Tim Hagenacker, Prof Dr
    • Principal Investigator: Tim Hagenacker, Prof Dr
  • Essen, Germany, 45131
    • Recruiting
    • Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH
    • Contact: Torsten Grehl, Dr
    • Principal Investigator: Torsten Grehl, Dr
  • Göttingen, Germany, 37075
    • Recruiting
    • Georg-August-Universität Göttingen Universitätsmedizin Göttingen
    • Contact: Jan Koch, PD Dr
    • Principal Investigator: Jan Koch, PD Dr
  • Hannover, Germany, 30625
    • Recruiting
    • Medizinische Hochschule Hannover
    • Contact: Susanne Petri, Prof Dr
    • Principal Investigator: Susanne Petri, Prof Dr
  • Jena, Germany, 07743
    • Recruiting
    • Universitätsklinikum Jena
    • Contact: Robert Steinbach, Dr
  • Leipzig, Germany, 04103
    • Recruiting
    • Universität Leipzig
    • Contact: Petra Baum, PD Dr
    • Principal Investigator: Petra Baum, PD Dr
  • Lübeck, Germany, 23538
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein
    • Contact: Julian Grosskreutz, Prof Dr
    • Principal Investigator: Julian Grosskreutz, Prof Dr
  • Mannheim, Germany, 68167
    • Recruiting
    • Universität Heidelberg Medizinische Fakultät Mannheim
    • Contact: Jochen Weishaupt, Prof Dr
    • Principal Investigator: Jochen Weishaupt, Prof Dr
  • München, Germany, 81675
    • Recruiting
    • Klinikum rechts der Isar der Technischen Universität München
    • Contact: Paul Lingor, Prof Dr
    • Principal Investigator: Paul Lingor, Prof Dr
  • Münster, Germany, 48149
    • Recruiting
    • Westfälische Wilhelms-Universität Münster
    • Contact: Matthias Boentert, PD DR
    • Principal Investigator: Matthias Boentert, PD Dr
  • Regensburg, Germany, 93053
    • Recruiting
    • Universitätsklinikum Regensburg
    • Contact: Zacharias Kohl, PD Dr
    • Principal Investigator: Zacharias Kohl, PD Dr
  • Rostock, Germany, 18057
    • Recruiting
    • Universitatsmedizin Rostock
    • Contact: Andreas Hermann, Prof. Dr. med. Dr. rer. med.
    • Principal Investigator: Andreas Hermann, Prof Dr Dr
  • Ulm, Germany, 89081
    • Recruiting
    • Universitatsklinikum Ulm
    • Contact: Johannes Dorst, Prof Dr
    • Principal Investigator: Johannes Dorst, Prof Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

patients with clinical diagnosis of amyotrophic lateral sclerosis

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Boris Canessa ALS Stiftung
• Investigators: Principal Investigator: Thomas Meyer, MD, Charite University, Berlin, Germany

Publications and helpful links

Helpful Links

• Website of principle investigator
• Website of funding organization

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 1, 2023
• First Submitted That Met QC Criteria: December 31, 2023
• First Posted (Estimated): January 11, 2024

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: December 31, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Progression; ALS; biomarker; Amyotrophic lateral sclerosis; Neurofilament light chain; NfL; ALS Funktional Rating Scale; treatment marker; therapeutic marker
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: NfL-ALS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No