Study of Predictive Factors of Progression of Motor Neurone Disease

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis; Motor Neuron Disease
• Interventions: Other: biomarkers (composite analysis)

• Registration Number: NCT02360891
• Lead Sponsor: University Hospital, Lille

Brief Summary

Amyotrophic lateral sclerosis (ALS) is a complex polymorph and devastating neurodegenerative disease. Although the pathophysiological mechanisms underlying the development of ALS remain to be fully elucidated, there have been significant advances in the understanding of ALS pathogenesis, with evidence emerging of a complex interaction between genetic factors and dysfunction of vital molecular pathways. However, the numerous randomized clinical trials (RCT) for ALS have failed to generate improved drug treatments. Biomarkers able to bring prognostic value and to distinguish the different endophenotypes of this polymorphic disease could help to better select clusters of patients in order to improve the RCT outcomes. However, little progress has been made in the development of viable diagnostic, prognostic and monitoring markers. This could be explained by common shortcomings, such as relatively small sample sizes, statistically underpowered study designs, lack of disease controls and poorly characterized patient cohorts. It is yet crucial that the investigators further develop and validate ALS biomarkers and incorporate these biomarkers into the drug development pipeline for ALS.

The aim of the present study is therefore to determine the clinical, biological, imaging, and electrophysiological biomarkers of prognosis of survival without events (i.e. severe comorbidity, 24 hours of non invasive ventilation, tracheotomy). This is a prospective observational multicentric French study of a cohort of 1000 ALS patients.

This large multimodal database will be open for international fruitful scientific collaborations.

Detailed Description

This is a prospective observational multicentric French study of a cohort of 1000 ALS patients, 100 neurological controls and 200 healthy controls followed from the first signs to the end of the disease.

The aim of the present study is therefore to determine the clinical, biological, imaging, and electrophysiological biomarkers of prognosis of survival without events (i.e. severe comorbidity, 24 hours of non invasive ventilation, tracheotomy).

Secondary objectives will notably include i) the biomarkers of disease progression ii) biomarkers of diagnosis as compared with controls iii) the determination of the different endophenotypes according to the prognosis, the genetic profiles and the initial clinical presentations. Criteria of assessment will notably include detailed medical history, habitus, past and present treatments, vascular risk factors, ALSFRS-R, muscular testing, respiratory parameters including early nocturnal saturation and apneal profile, the detailed and predetermined clinical presentations, extensive cognitive and behavioral examination, extensive blood, cerebrospinal fluid, urines biological tests, genetic analyses, multiple brain and spinal MRI sequences, and electrophysiological tests (i.e. electromyogram, MUNIX, triple stimulation). Invasive tests will be optional (i.e. lumbar puncture, skin biopsies, muscular biopsies).

The large number of patients will allow in depth statistical analyses, notably to establish decisional trees (CHAID).

Study Timeline

• Study First Submitted: 2015-01-07
• Study Start: 2015-01-12
• Study First Submitted QC: 2015-02-10
• Study First Posted: 2015-02-11
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-04
• Last Update Posted: 2022-11-07
• Primary Completion: 2026-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Not provided

Exclusion Criteria

• Subjects younger than 18 years
• Patient unable to provide informed consent
• Having severe disease or life- functional prognosis
• Contraindications MRI

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
neurological controls	biomarkers (composite analysis)	patients with other neurological disease
patients	biomarkers (composite analysis)	follow up of patients with amyotrophic lateral sclerosis from the first signs to the end of the disease
healthy controls	biomarkers (composite analysis)	age matched healthy controls

Primary Outcome Measures

Name	Time	Method
Change of biomarkers of survival	From date of randomization until the date of first documented progression , assessed up to 100 months	The predictive value of the clinical, biological, imaging, and electrophysiological biomarkers of survival will be analyzed according to the life duration (months) without events (i.e. severe comorbidity, 24 hours of non invasive ventilation, tracheotomy)

Secondary Outcome Measures

Name	Time	Method
Change of biomarkers of disease progression	baseline, 3 months, 6 months, 9 months, 12 months, 15 months, 24 months, 36 months, 48 months (average)	The predictive value of the clinical, biological, imaging, and electrophysiological biomarkers of prognosis will be analyzed according to the rate of progression of the ALSFRS-R score
Clinical endophenotypes according to the survival duration	From date of randomization until the date of death related with ALS or tracheotomy or continuous non invasive ventilation (24 hours a day), whichever came first, assessed up to 100 months	The determination of the different clinical, biological, radiological and electrophysiological endophenotypes (clusters of the same characteristics) according to the survival duration
Genetic endophenotypes	the date of death related with ALS or tracheotomy or continuous non invasive ventilation (24 hours a day), whichever came first, assessed up to 100 months	the determination of the different clinical, biological, radiological and electrophysiological endophenotypes (clusters of the same characteristics) according to the according to the genetic forms (SOD1, TDP43, FUS, C9orf72,...)

Trial Locations

Locations (13)

Hôpital de l'Archet 1, CHU; 🇫🇷 Nice, France

CHU Pontchaillou; 🇫🇷 Angers, France

CHU Cote de Nacre; 🇫🇷 Caen, France

CHU Gabriel Montpied; 🇫🇷 Clermont-Ferrand, France

CHRU, Hôpital Salengro; 🇫🇷 Lille, France

Hôpital Dupuytren; 🇫🇷 Limoges, France

AP-HM,Hôpital de la Timone; 🇫🇷 Marseille, France

Hôpital Gui de Chauliac; 🇫🇷 Montpellier, France

Hôpital Neurologique Pierre Wertheimer; 🇫🇷 Lyon, France

Centre Hospitalier; 🇫🇷 Saint Brieuc, France

Hôpital Nord; 🇫🇷 Saint Etienne, France

CHU Bretonneau; 🇫🇷 Tours, France

Hôpital La Pitié (AP-HP); 🇫🇷 Paris, France