Presymptomatic Neuromuscular Junction Defects and Compensatory Mechanisms in ALS (PRE-ALS)
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|ClinicalTrials.gov Identifier: NCT03573466|
Recruitment Status : Recruiting
First Posted : June 29, 2018
Last Update Posted : August 18, 2020
Denervation of neuromuscular junctions (NMJs) and initial compensatory reinnervation is the earliest pathological event in various motor neuron disease models, occurring far before motor symptom onset. In patients harboring genetic mutations responsible for Amyotrophic Lateral Sclerosis (ALS), identification of early, pre-symptomatic, NMJ pathological events and compensatory mechanisms could lead to the development of new treatments to prevent motor functional impairment.
The aims of our study are thus:
- To investigate and characterize early, presymptomatic, defects of NMJ morphology in pre-manifest C9ORF72 or SOD1 mutation carriers;
- To investigate and quantify reinnervation at the level of NMJs in these subjects;
- To identify muscle molecular dysregulated pathways involved in the development of NMJ alterations and the development / maintenance of compensatory collateral reinnervation.
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Procedure: Muscle biopsy||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Presymptomatic Neuromuscular Junction Defects and Compensatory Mechanisms in Amyotrophic Lateral Sclerosis (ALS)|
|Actual Study Start Date :||April 10, 2019|
|Estimated Primary Completion Date :||October 10, 2021|
|Estimated Study Completion Date :||December 1, 2021|
|Experimental: Amyotrophic Lateral Sclerosis||
Procedure: Muscle biopsy
A motor point biopsy of deltoid muscle will be carried out at the time of inclusion using a standardized procedure, as routinely performed. Muscle samples will be removed from the deltoid muscle by open biopsy under local anaesthesia. The region containing NMJs will be determined by the small twitch provoked by the tip of the scalpel on the surface of the muscle fascicles.
- Quantification of neuromuscular junctions innervation [ Time Frame: 18 month ]Quantification of innervation by confocal microscopy will be performed by classifying neuromuscular junctions observed in each biopsy specimen according to the relationship between the intrasynaptic axonal branches and the postsynaptic membrane in four categories: "normal", "denervated", "partially innervated", or "reinnervated"
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): NCT03573466
|Contact: Gaelle BRUNETEAU, MD, PhD||+33 1 42 16 24 email@example.com|
|Principal Investigator:||Gaelle BRUNETEAU, BRUNETEAU||APHP|