Presymptomatic Neuromuscular Junction Defects and Compensatory Mechanisms in ALS

NCT03573466 | Unknown

• 2 other identifiers: P171004J2018-A00573-52
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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:

1. 1.To investigate and characterize early, presymptomatic, defects of NMJ morphology in pre-manifest C9ORF72 or SOD1 mutation carriers;
2. 2.To investigate and quantify reinnervation at the level of NMJs in these subjects;
3. 3.To identify muscle molecular dysregulated pathways involved in the development of NMJ alterations and the development / maintenance of compensatory collateral reinnervation.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Motor Neuron; Neuromuscular Junction

Outcome Measures

Primary Outcomes (1)

• Quantification of neuromuscular junctions innervation

  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"

  18 month

Study Arms (1)

Amyotrophic Lateral Sclerosis

EXPERIMENTAL

Procedure: Muscle biopsy

Interventions

Muscle biopsy PROCEDURE

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.

Amyotrophic Lateral Sclerosis

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects harboring a mutation in C9ORF72 or SOD1 gene
• Without any functional motor complaint and clinical motor deficit at neurological examination
• Aged 30 to 70 (inclusive).
• Patients covered by the social insurance system

You may not qualify if:

• Any motor deficit
• Any significant cognitive or psychiatric impairment leading to limitation in decision making capacity
• Inability to give informed consent
• Patient unable to contact or to be contacted by the investigator in case of emergency
• Women who are pregnant or nursing, or without effective contraceptive method
• Concomitant medication contraindicating muscle biopsy (platelet suppressive agents, oral anticoagulant therapy)
• Medical condition contraindicating muscle biopsy (hypocoagulative disease, allergy to anaesthetic drugs, acute intermittent porphyria)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Gaelle BRUNETEAU, BRUNETEAU

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: June 29, 2018
• Study Start: April 10, 2019
• Primary Completion: May 25, 2023
• Study Completion: May 25, 2023
• Last Updated: February 18, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)