Frequency of SOD1 and C9orf72 Gene Mutations in French ALS (GENIALS)

The purpose of the study is to determine the frequency of mutations in the C9orf72 and SOD1 genes in the incident population of ALS patients followed in the FILSLAN centres

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Genetic: Blood

Detailed Description

After obtaining free and informed consent for genetic characteristic tests, a blood sample will be taken during hospitalisation for diagnostic confirmation or during the quarterly multidisciplinary consultations planned for these patients in the classic follow-up set up within the ALS centres of the FILSLAN network if the genetic status is not already known. This sample will be integrated into the standard management of ALS patients, which includes a neurological examination and paraclinical explorations, including a biological assessment.

The patient will then be reviewed during the standard multidisciplinary follow-up consultations. Information to the patient on his or her C9orf72 or SOD1 genetic status will be included in the quarterly multidisciplinary consultations for the classic follow-up of ALS patients.

It should also be noted that the data (ALSFRS-r score, weight, FEV) collected during the 6 and 12 month consultations will be processed for the purposes of this research.

For patients included in the quarterly multidisciplinary consultations planned in the classic follow-up, if the genetic blood sample was taken during the initial hospitalisation for diagnosis, then it will not be repeated in the framework of the research. In this case, the genetic status of C9orf72 or SOD1 will be available at the inclusion visit and the patient will receive specific information about his or her genetic status.

Consent for the research will nevertheless be obtained in order to have the patient's agreement to the processing of their health data for the purposes of the research at inclusion, 6 months and 12 months.

• Study Type: Observational
• Enrollment (Actual): 1000

Contacts and Locations

Study Locations

• France
  • Angers, France, 49000
    • CHU Angers
  • Bordeaux, France, 33000
    • CHU Bordeaux
  • Brest, France, 29200
    • CHU de Brest
  • Bron, France, 69677
    • CHU Lyon
  • Caen, France, 14000
    • CHU Caen
  • Clermont-Ferrand, France, 63000
    • CHU Clermont Ferrand
  • Dijon, France, 21000
    • CHU Dijon
  • Lille, France, 59000
    • CHU Lille
  • Limoges, France, 87000
    • CHU Limoges
  • Marseille, France, 13000
    • CHU Marseille
  • Montpellier, France, 34000
    • CHU Montpellier
  • Nancy, France, 54000
    • CHU Nancy
  • Nice, France, 06000
    • CHU Nice
  • Paris, France, 75000
    • Paris - Groupe hospitalier de la Pitié Salpetrière
  • Rennes, France, 35033
    • CHU de Rennes
  • Saint-Pierre, France, 97448
    • CHU La Réunion
  • Saint-Priest-en-Jarez, France, 42270
    • CHU St Etienne
  • Strasbourg, France, 67000
    • CHU Strasbourg
  • Toulouse, France, 31000
    • CHU Toulouse
  • Tours, France, 37000
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

incident population of ALS patients followed in the FILSLAN centres.

Description

Inclusion Criteria:

• Adult aged ≥ 18 years old
• ALS defined, probable or likely based on neurophysiological data according to Airlie House criteria (Brooks, 2000)
• Sporadic ALS or familial ALS defined by the existence of a case of ALS or FTD among first or second degree relatives of the patient included (Byrne et al, 2011).
• Participant affiliated to a social security scheme
• Free, informed and signed consent for the examination of the genetic characteristics of the participant

Exclusion Criteria:

• All conditions mimicking ALS including motor neuropathies with multiple conduction blocks and all cases of ALS that do not meet the criteria of the Airlie House classification.
• Patients who are cognitively incapable of signing the consent to participate in this study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

adult patients with ALS; incident population of ALS patients followed in the FILSLAN centres.

Genetic: Blood; a blood sample will be taken during hospitalisation for diagnostic confirmation or during the quarterly multidisciplinary consultations scheduled as part of the standard follow-up set up for these patients in the ALS centres of the FILSLAN network. If the genetic status is not yet known, this sample will be taken (1 tube of 7mL EDTA) and then sent within 24-48 hours at room temperature to one of the 3 participating molecular biology laboratories according to the criteria defined in the manual of samples being taken in the 3 laboratories.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
genetic characteristics	frequency of mutations in the C9orf72 and SOD1 genes in the ALS patient population having follow-up for care within the FILSLAN centers French network	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neurological examination	describe phenotype of ALS patients according to their genetic status with a neurological examination	12 months
ALSFRS-r score	describe homogenous groups of ALS regarding ALSFRS-r score : slope of evolution of the ALSFRS-r score	12 months
weight	describe homogenous groups of ALS regarding weight in kg	12 months
Expiratory volume	describe homogenous groups of ALS regarding expiratory volume (FEV and LVC) in theoretical %.	12 months
Therapeutic management	Calculate the average time elapsed between the request for a molecular diagnosis by the ALS centre and the sending of the result. This will demonstrate the fluidity of the procedure and the ability to quickly inform the patient and the requesting clinician of the genetic status which will be essential to rapidly include patients in targeted gene therapy trials.	Baseline
Integration of the molecular study into the routine work-up	Compare the percentage of patients who have received genetic analysis to the number of new cases diagnosed in the ALS centres.	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Collaborators: Biogen
• Investigators: Principal Investigator: Philippe CORCIA, University Hospital, Tours

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): May 15, 2023

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Blood sample; Genetic features
• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: RIPH3-RNI20-GENIALS

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