Neuromuscular Transmission in Amyotrophic Lateral Sclerosis (NETALS)

November 16, 2012 updated by: Assistance Publique - Hôpitaux de Paris
Consistent data suggest that neuromuscular transmission is impaired in ALS patients. Neuromuscular junctions dysfunction may appear very early in the disease, as shown by data in animal models. The pathogenesis of this neuromuscular transmission impairment is unknown. Nogo A isoform, a possible marker of the disease over-expressed in skeletal muscle of ALS patients, can be involved. We will characterize the pathophysiological mechanisms implicated using a complete study of the structure and function of the NMJ on muscle biopsies, in a group of 20 ALS patients compared to 10 controls.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder involving motor neurons of the motor cortex, brain stem and spinal cord. Its pathogenesis remains unknown, and the only drug currently available, riluzole, only modestly prolongs survival. Consistent data show that neuromuscular transmission is impaired in patients with ALS. The significance of these abnormalities remains unknown, but recent data suggest that they potentially play a key role in the pathogenesis of the disease. Neuromuscular junctions (NMJs) dysfunction may appear very early in the disease, as shown by data in animal models. The mechanisms of this neuromuscular transmission impairment are unknown. Nogo A belonging to the family of neurite outgrowth inhibitor proteins which is abnormally expressed in skeletal muscle of ALS patients, is probably involved as it has been shown that over-expression of Nogo A in wild-type muscle leads to destabilization of NMJs. A detailed study of the structure and function of the NMJ in ALS patient is mandatory to better characterize the pathophysiological mechanisms implicated.

The aim of this study is to characterize the neuromuscular transmission dysfunction in ALS. For this purpose, we will study the structural and functional features of NMJs on muscle biopsies in a group of 20 ALS patients compared to 10 controls. Using biopsies of a vestigial muscle, the anconeus, we will perform a morphological study of the NMJ, including routine histochemistry, immunohistochemical studies for NMJ major proteins and immune IgG complexes and electron microscopy study. The number of acetylcholine receptors per endplate will be determined by radiolabeled alpha-bungarotoxin binding. Expression levels of Nogo-A will be determined in muscle specimens by western blot. Synaptic transmission at individual NMJs will also be studied ex vivo. We will record membrane potential over time using different nerve stimulation frequencies and we will analyze the properties of the miniature endplate potentials (spontaneous release of acetylcholine) and endplate potentials after stimulation of the nerve (evoked release of acetylcholine). The results of this structural and functional study of NMJ on muscle biopsy will be correlated with surface-EMG and clinical data.

This study will help identifying new mechanisms involved in the pathophysiology of ALS and potential new targets for future treatments.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75003
        • Bruneteau Gaelle

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  1. ALS patients:

    Inclusion criteria :

    • Aged 18 to 75 (inclusive)
    • Possible, probable (clinically or laboratory) or definite ALS according to the revised El Escorial criteria
    • Duration of the disease of less then 12 months
    • Willing and able to provide a written informed consent
    • With french social insurance affiliation

    Exclusion criteria :

    • Cognitive changes or psychiatric condition, 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
    • concomitant medication contraindicating muscular biopsy (platelet suppressive agents if treatment can not medically be stopped 2 weeks before surgical procedure, oral anticoagulant therapy)
    • medical condition contraindicating muscular biopsy (hypo-coagulative disease, allergy to anaesthetic drugs)
    • medical condition susceptible to influence on EMG examination (concomitant neurological or rheumatological disease)

  2. Controls:

    • adult patients (minimum 18y) without neuromuscular disease
    • undergoing elbow surgery for local joint or bone disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: 2
control subjects with muscle biopsy
Procedure: Anconeus Muscle biopsy
Anconeus muscle specimens will be surgically removed. The biopsy will be performed under regional anaesthesia and will require an about 5 cm incision of the skin and muscle fascia from the lateral condyle to over the ridge of the proximal ulna, 3 or 4 cm distal to the tip of the olecranon. A triangular muscle flap will be removed, and then the fascia and skin will be closed with running dissolving suture.
OTHER: 1
ALS patients with muscle biopsy
Procedure: Anconeus Muscle biopsy
Anconeus muscle specimens will be surgically removed. The biopsy will be performed under regional anaesthesia and will require an about 5 cm incision of the skin and muscle fascia from the lateral condyle to over the ridge of the proximal ulna, 3 or 4 cm distal to the tip of the olecranon. A triangular muscle flap will be removed, and then the fascia and skin will be closed with running dissolving suture.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Characterization of the neuromuscular transmission dysfunction in ALS by studying the structural and functional features of NMJs on muscle biopsies
Time Frame: within the 15 days after inclusion (month 0 = M0)
within the 15 days after inclusion (month 0 = M0)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Search for correlations between the results of the structural and functional study of neuromuscular junctions on muscle biopsy and surface-EMG and clinical data
Time Frame: at M0, M3, M6
at M0, M3, M6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Association Française contre les Myopathies (AFM), Paris
Association pour la Recherche sur la Sclérose Latérale Amyotrophique

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gaelle Bruneteau, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2009

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2012

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 11, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2009

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 19, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 19, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P080404

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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