Clinical trial NCT06201650: Neurofilament Light Chain in Amyotrophic Lateral Sclerosis
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Keywords: ALS
Amyotrophic lateral sclerosis
Neurofilament light chain
NfL
ALS Funktional Rating Scale
Progression
biomarker
treatment marker
therapeutic marker
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Boris Canessa ALS Stiftung
First posted: 2024-01-11
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: patients with clinical diagnosis of amyotrophic lateral sclerosis

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: correlation of serum neurofilament light chain to ALS progression
timeFrame: 2020-2024
measure: correlation of serum neurofilament light chain with ALS phenotypes
timeFrame: 2020-2024
measure: correlation of serum neurofilament light chain with ALS treatment options
timeFrame: 2020-2024
Secondary outcomes:
measure: correlation of serum neurofilament light chain with non-pharmacologic ALS interventions
timeFrame: 2022-2024
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Berlin
country: Germany
facility: Vivantes Klinikum Kaulsdorf
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Dresden
country: Germany
facility: Technische Universität Dresden
city: Essen
country: Germany
facility: Alfried Krupp von Bohlen und Halbach Krankenhaus gGmbH
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Göttingen
country: Germany
facility: Georg-August-Universität Göttingen Universitätsmedizin Göttingen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Leipzig
country: Germany
facility: Universität Leipzig
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Mannheim
country: Germany
facility: Universität Heidelberg Medizinische Fakultät Mannheim
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Münster
country: Germany
facility: Westfälische Wilhelms-Universität Münster
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
affiliation: Charite University, Berlin, Germany
name: Thomas Meyer, MD
role: PRINCIPAL_INVESTIGATOR
References: