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

• ClinicalTrials.gov Identifier: NCT06201650
• Recruitment Status: Recruiting
• First Posted: January 11, 2024
• Last Update Posted: January 11, 2024
• Sponsor: Charite University, Berlin, Germany
• Collaborator: Boris Canessa ALS Stiftung
• Information provided by (Responsible Party): Thomas Meyer, MD, Charite University, Berlin, Germany

Tracking Information

• First Submitted Date: April 1, 2023
• First Posted Date: January 11, 2024
• Last Update Posted Date: January 11, 2024
• Actual Study Start Date: November 11, 2020
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 31, 2023)

• correlation of serum neurofilament light chain to ALS progression [ Time Frame: 2020-2024 ]
  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)
• correlation of serum neurofilament light chain with ALS phenotypes [ Time Frame: 2020-2024 ]
  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
• correlation of serum neurofilament light chain with ALS treatment options [ Time Frame: 2020-2024 ]
  correlation of serum neurofilament light chain to ALS interventions such as treatment with tofersen and other medicines

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: December 31, 2023)

correlation of serum neurofilament light chain with non-pharmacologic ALS interventions [ Time Frame: 2022-2024 ]

correlation of serum neurofilament light chain with non-pharmacologic ALS interventions including nutrition or ventilation treatment

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Serum

• Sampling Method: Probability Sample
• Study Population: patients with clinical diagnosis of amyotrophic lateral sclerosis

Condition

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Diagnostic Test: Neurofilament light chain

Neurofilament light chain as biomarker for amyotrophic lateral sclerosis

• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 31, 2023): 3000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Thomas Meyer, MD; 004930450560028; thomas.meyer@charite.de

Contact: Péter Körtvélyessy, MD; 004930450560028; peter.koertvelyessy@charite.de

• Listed Location Countries: Austria, Germany

Administrative Information

• NCT Number: NCT06201650
• Other Study ID Numbers: NfL-ALS
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Thomas Meyer, MD, Charite University, Berlin, Germany
• Original Responsible Party: Same as current
• Current Study Sponsor: Charite University, Berlin, Germany
• Original Study Sponsor: Same as current
• Collaborators: Boris Canessa ALS Stiftung

Investigators

• Principal Investigator: Thomas Meyer, MD; Charite University, Berlin, Germany

• PRS Account: Charite University, Berlin, Germany
• Verification Date: December 2023