Study of Predictive Factors of Progression of Motor Neurone Disease

Amyotrophic Lateral Sclerosis Clinical Trial

— PULSE  

Official title:

Study of Predictive Factors of Progression of Motor Neurone Disease Prognosis and Endophenotype Biomarkers French Database Set up

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02360891
• Other study ID #: 2012-50
• Secondary ID: 2013-A00969-36
• Status: Recruiting
• Start date: January 12, 2015
• Est. completion date: January 2026

Study information

• Verified date: November 2022
• Source: University Hospital, Lille
• Contact: David Devos, MD, PhD
• Email: david.devos[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria for ALS patients:

• 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

Inclusion Criteria for healthy controls:

• 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

Inclusion Criteria for neurological controls:

• 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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Other:
• biomarkers (composite analysis)
biological, imaging, electrophysiological and anatomopathological examinations

Locations

Country	Name	City	State
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	Hôpital Neurologique Pierre Wertheimer	Lyon
France	AP-HM,Hôpital de la Timone	Marseille
France	Hôpital Gui de Chauliac	Montpellier
France	Hôpital de l'Archet 1, CHU	Nice
France	Hôpital La Pitié (AP-HP)	Paris
France	Centre Hospitalier	Saint Brieuc
France	Hôpital Nord	Saint Etienne
France	CHU Bretonneau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change of biomarkers of disease progression	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	baseline, 3 months, 6 months, 9 months, 12 months, 15 months, 24 months, 36 months, 48 months (average)
Secondary	Clinical endophenotypes according to the survival duration	The determination of the different clinical, biological, radiological and electrophysiological endophenotypes (clusters of the same characteristics) 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
Secondary	Genetic endophenotypes	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,...)	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