Clinical Characteristics, Natural History, Health Care Measures, and Genetic Screening in Patients With ALS (ID-ALS)

Clinical Characteristics, Natural History, Health Care Measures, and the Frequency of Genetic Variants in the Genes of SOD1, C9orf72, FUS and TARDBP in Patients With Sporadic and Familial Amyotrophic Lateral Sclerosis (ALS)

Patients with sporadic ALS (sALS), which refers to those without a family history of ALS, are typically not subjected to genetic investigations as part of their standard care. Therefore, their mutation status is often unknown. Even patients with familial ALS (fALS), who have a known family history of ALS, are not regularly screened for genetic mutations. This project aims to study a large group of ALS patients, examining their family history, clinical characteristics, healthcare measures, and genetic variants in ALS's most commonly mutated genes: SOD1, C9orf72, FUS, and TARDBP. Examining genetically distinct ALS cohorts is significant, as understanding the relationship between genotype and disease progression is essential in determining the therapeutic potential of future genetic therapies.

Study Overview

• Status: Completed
• Conditions: Motor Neuron Disease, Amyotrophic Lateral Sclerosis

Detailed Description

Only limited data are available on the frequency of genetic variants in patients with sporadic ALS (sALS) and familial ALS (fALS). Genetic investigations do not belong to the standard of care in patients with sALS (patients without a family history of ALS). As a result, the patient's mutation status is commonly unknown. Even in patients with fALS (with a known family history of ALS), screening for genetic mutations is not performed regularly due to lacking treatment options in gene therapy. However, this paradigm is about to change as clinical trials on genetic medicines are ongoing and might result in the approval of new genetically investigated drugs. This project aims to explore a large cohort of ALS patients on family history, clinical characteristics, healthcare measures, and genetic variants in SOD1, C9orf72, FUS, and TARDBP - the most commonly mutated genes in ALS. This cohort study will allow us to determine the frequency of gene mutations in ALS patients in a real-world setting of ALS centers in Germany. Furthermore, the project shall enhance insights into potential differences between genetically defined cohorts using the course of the disease and the provision of health care measures. The investigation of genetically distinct ALS cohorts is particularly relevant, as an improved understanding of the relationship between the genotype and the journey of disease is scientifically indispensable to determine the therapeutic potential of future genetic therapies.

• Study Type: Observational
• Enrollment (Actual): 2000

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Center for ALS and other motor neuron disorders, Charité - Universitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The enrollment of subjects takes place in specialized ALS outpatient centers in Germany. ALS patients eligible for the investigation will be invited to participate in this cohort study. After obtaining informed consent, subjects will be enrolled in the study.

Description

Inclusion Criteria:

• ALS, including classical ALS, Progressive Muscle atrophy (PMA) or Primary Lateral Sclerosis (PLS)
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) under national and local subject privacy regulations
• Age of 18 years old at the time of informed consent

Exclusion Criteria:

• Inability to provide patient directives about the notification of individual study results on genetic variants of SOD1, C9orf72, FUS and TARDBP
• Inability to comply with study requirements
• Unspecified reasons that, in the opinion of the site investigator, perceive the subject as unsuitable for enrollment

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variants in the genes of SOD1, C9orf72, FUS and TARDBP	• To identify the frequency of genetic variants in the genes of SOD1, C9orf72, FUS and TARDBP in patients with sALS and fALS	2 years

Collaborators and Investigators

• Sponsor: Ambulanzpartner Soziotechnologie APST GmbH
• Collaborators: Charite University, Berlin, Germany
• Investigators: Study Director: Thomas Meyer, Prof. Dr., Center for ALS and other motor neuron disorders, Charité - Universitätsmedizin Berlin

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: April 28, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Biomarker; C9orf72; SOD1; TARDBP; FUS; ALSFRS-R; ID-ALS; ALSFRS-R-SE; Neurofilament light chain NfL; APST Research; ALS-App
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 400634

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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