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Study of Predictive Factors of Progression of Motor Neurone Disease (PULSE)

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ClinicalTrials.gov Identifier: NCT02360891
Recruitment Status : Recruiting
First Posted : February 11, 2015
Last Update Posted : October 6, 2021
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment
Amyotrophic Lateral Sclerosis Motor Neuron Disease Other: biomarkers (composite analysis)

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).

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 10 Years
Official Title: Study of Predictive Factors of Progression of Motor Neurone Disease Prognosis and Endophenotype Biomarkers French Database Set up
Actual Study Start Date : January 12, 2015
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : January 2026


Group/Cohort Intervention/treatment
patients
follow up of patients with amyotrophic lateral sclerosis from the first signs to the end of the disease
Other: biomarkers (composite analysis)
biological, imaging, electrophysiological and anatomopathological examinations

neurological controls
patients with other neurological disease
Other: biomarkers (composite analysis)
biological, imaging, electrophysiological and anatomopathological examinations

healthy controls
age matched healthy controls
Other: biomarkers (composite analysis)
biological, imaging, electrophysiological and anatomopathological examinations




Primary Outcome Measures :
  1. Change of biomarkers of survival [ Time Frame: 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 :
  1. Change of biomarkers of disease progression [ Time Frame: 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

  2. Clinical endophenotypes according to the survival duration [ Time Frame: 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

  3. Genetic endophenotypes [ Time Frame: 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,...)


Biospecimen Retention:   Samples With DNA
whole blood, serum, white cells, platelets, cerebrospinal fluid,skin, muscle, brains


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Multicentric French cohort of 1000 ALS patients, 100 neurological controls and 200 healthy controls
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02360891


Contacts
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Contact: David Devos, MD, PhD david.devos@chru-lille.fr

Locations
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France
CHU Pontchaillou Recruiting
Angers, France
Principal Investigator: Dominique Maugin, MD,PhD         
CHU Cote de Nacre Recruiting
Caen, France
Principal Investigator: Fausto Viader, MD         
CHU Gabriel Montpied Recruiting
Clermont-Ferrand, France
Principal Investigator: Nathalie Guy, MD         
CHRU, Hôpital Salengro Recruiting
Lille, France
Contact: David Devos, MD, PhD       david.devos@chru-lille.fr   
Principal Investigator: David Devos, MD, PhD         
Hôpital Dupuytren Recruiting
Limoges, France
Principal Investigator: Philippe Couratier, MD         
Hôpital Neurologique Pierre Wertheimer Recruiting
Lyon, France
Principal Investigator: Emilien Bernard, MD,PhD         
AP-HM,Hôpital de la Timone Recruiting
Marseille, France
Principal Investigator: Attarian Shahram, MD,PhD         
Hôpital Gui de Chauliac Recruiting
Montpellier, France
Principal Investigator: William Camu, MD         
Hôpital de l'Archet 1, CHU Recruiting
Nice, France
Hôpital La Pitié (AP-HP) Recruiting
Paris, France
Principal Investigator: François Salachas, MD         
Centre Hospitalier Recruiting
Saint Brieuc, France
Principal Investigator: Yvan Kolev, MD         
Hôpital Nord Recruiting
Saint Etienne, France
Principal Investigator: Jean-Christophe Antoine, MD,PhD         
CHU Bretonneau Recruiting
Tours, France
Principal Investigator: Philippe Corcia, MD         
Sponsors and Collaborators
University Hospital, Lille
Investigators
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Study Chair: David Devos, MD, PhD University Hospital, Lille
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT02360891    
Other Study ID Numbers: 2012-50
2013-A00969-36 ( Other Identifier: ID RCB number, ANSM )
First Posted: February 11, 2015    Key Record Dates
Last Update Posted: October 6, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Lille:
multimodal biomarkers
prognosis
endophenotypes
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases