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Presymptomatic Neuromuscular Junction Defects and Compensatory Mechanisms in ALS (PRE-ALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03573466
Recruitment Status : Active, not recruiting
First Posted : June 29, 2018
Last Update Posted : February 18, 2022
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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. To investigate and characterize early, presymptomatic, defects of NMJ morphology in pre-manifest C9ORF72 or SOD1 mutation carriers;
  2. To investigate and quantify reinnervation at the level of NMJs in these subjects;
  3. 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
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 : May 25, 2023
Estimated Study Completion Date : May 25, 2023

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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"

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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion criteria:

  • 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)

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): NCT03573466

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Pitié-Salpêtrière Hospital
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Gaelle BRUNETEAU, BRUNETEAU APHP
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03573466    
Other Study ID Numbers: P171004J
2018-A00573-52 ( Other Identifier: ANSM )
First Posted: June 29, 2018    Key Record Dates
Last Update Posted: February 18, 2022
Last Verified: February 2022
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 Assistance Publique - Hôpitaux de Paris:
Motor Neuron
Neuromuscular Junction
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases