Study of Predictive Factors of Progression of Motor Neurone Disease

NCT02360891 | Completed DMC

• 2 other identifiers: 2012-502013-A00969-36
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 13

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.

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Keywords

multimodal biomarkers; prognosis; endophenotypes

Outcome Measures

Primary Outcomes (1)

• Change of biomarkers of survival

  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)

  From date of randomization until the date of first documented progression , assessed up to 100 months

Secondary Outcomes (3)

• Change of biomarkers of disease progression

  baseline, 3 months, 6 months, 9 months, 12 months, 15 months, 24 months, 36 months, 48 months (average)

• 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

• 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

Study Arms (3)

patients

follow up of patients with amyotrophic lateral sclerosis from the first signs to the end of the disease

Other: biomarkers (composite analysis)

neurological controls

patients with other neurological disease

Other: biomarkers (composite analysis)

healthy controls

age matched healthy controls

Other: biomarkers (composite analysis)

Interventions

biomarkers (composite analysis) OTHER

biological, imaging, electrophysiological and anatomopathological examinations

healthy controls; neurological controls; patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Multicentric French cohort of 1000 ALS patients, 100 neurological controls and 200 healthy controls

You may qualify if:

• Patients with suspicion of Amyotrophic lateral sclerosis
• Since the first signs (cramps fasciculation) or first deficit at the diagnosis work up
• Patient older than 18 years
• Patient able to provide informed consent
• Subjects older than 18 years (matched population for age and sex with ALS)
• Neurological testing and examination showing no neurological disorders.
• Not having severe disease or life- functional prognosis
• Patients having a typical neurodegenerative diseases other than ALS (Parkinson's disease, Alzheimer's disease)
• Not having severe disease or life- functional prognosis
• Patient older than 18 years (matched population for age and sex with ALS)
• Patient able to provide informed consent

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (13)

CHU Pontchaillou

Angers, France

Location

CHU Cote de Nacre

Caen, France

Location

CHU Gabriel Montpied

Clermont-Ferrand, France

Location

CHRU, Hôpital Salengro

Lille, France

Location

Hôpital Dupuytren

Limoges, France

Location

Hôpital Neurologique Pierre Wertheimer

Lyon, France

Location

AP-HM,Hôpital de la Timone

Marseille, France

Location

Hôpital Gui de Chauliac

Montpellier, France

Location

Hôpital de l'Archet 1, CHU

Nice, France

Location

Hôpital La Pitié (AP-HP)

Paris, France

Location

Centre Hospitalier

Saint-Brieuc, France

Location

Hôpital Nord

Saint-Etienne, France

Location

CHU Bretonneau

Tours, France

Location

Related Publications (3)

• Grolez G, Kyheng M, Lopes R, Moreau C, Timmerman K, Auger F, Kuchcinski G, Duhamel A, Jissendi-Tchofo P, Besson P, Laloux C, Petrault M, Devedjian JC, Perez T, Pradat PF, Defebvre L, Bordet R, Danel-Brunaud V, Devos D. MRI of the cervical spinal cord predicts respiratory dysfunction in ALS. Sci Rep. 2018 Jan 29;8(1):1828. doi: 10.1038/s41598-018-19938-2.

  PMID: 29379040 RESULT

• Grapperon AM, Harlay V, Boucekine M, Devos D, Rolland AS, Desnuelle C, Delmont E, Verschueren A, Attarian S. Could the motor unit number index be an early prognostic biomarker for amyotrophic lateral sclerosis? Clin Neurophysiol. 2024 Jul;163:47-55. doi: 10.1016/j.clinph.2024.04.013. Epub 2024 Apr 26.

  PMID: 38703699 DERIVED

• Le Gall L, Duddy WJ, Martinat C, Mariot V, Connolly O, Milla V, Anakor E, Ouandaogo ZG, Millecamps S, Laine J, Vijayakumar UG, Knoblach S, Raoul C, Lucas O, Loeffler JP, Bede P, Behin A, Blasco H, Bruneteau G, Del Mar Amador M, Devos D, Henriques A, Hesters A, Lacomblez L, Laforet P, Langlet T, Leblanc P, Le Forestier N, Maisonobe T, Meininger V, Robelin L, Salachas F, Stojkovic T, Querin G, Dumonceaux J, Butler Browne G, Gonzalez De Aguilar JL, Duguez S, Pradat PF. Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles. J Cachexia Sarcopenia Muscle. 2022 Apr;13(2):1385-1402. doi: 10.1002/jcsm.12945. Epub 2022 Feb 22.

  PMID: 35194965 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, serum, white cells, platelets, cerebrospinal fluid,skin, muscle, brains

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Biomarkers

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biological Factors

Study Officials

• David Devos, MD, PhD

  University Hospital, Lille

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2015
• First Posted: February 11, 2015
• Study Start: January 12, 2015
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)