Amyotrophic Lateral SclerosisNETALSNCT00847847
Neuromuscular Transmission in Amyotrophic Lateral Sclerosis
A study testing Anconeus Muscle biopsy in people with Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Anconeus Muscle biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2009to Apr 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- Controls:
- adult patients (minimum 18y) without neuromuscular disease
- undergoing elbow surgery for local joint or bone disease
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Anconeus Muscle biopsy
- Keywords
- ALS, Motor neuron, Pathophysiology, Neuromuscular junction, Neuromuscular transmission, Microelectrodes
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anconeus Muscle biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 2 | Other | control subjects with muscle biopsy Receives: Procedure: Anconeus Muscle biopsy |
| 1 | Other | ALS patients with muscle biopsy Receives: Procedure: Anconeus Muscle biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterization of the neuromuscular transmission dysfunction in ALS by studying the structural and functional features of NMJs on muscle biopsies
Measured: within the 15 days after inclusion (month 0 = M0)
Secondary outcomes (1)
Search for correlations between the results of the structural and functional study of neuromuscular junctions on muscle biopsy and surface-EMG and clinical data
Measured: at M0, M3, M6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2009 (estimated)
- Study startMar 2009
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Association pour la Recherche sur la Sclérose Latérale Amyotrophique, Association Française contre les Myopathies (AFM), Paris
- Responsible party
- Sponsor
- Investigators
- Gaelle Bruneteau, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00847847
- Sponsor's protocol ID
- P080404
- Acronym
- NETALS
- Status last verified
- Dec 2009
- First submitted
- 11 Feb 2009
- Last updated
- 19 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromuscular Transmission in Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT00847847
- Acronym / sponsor ID
- NETALS / P080404
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Motor neuron, Pathophysiology, Neuromuscular junction, Neuromuscular transmission, Microelectrodes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Association pour la Recherche sur la Sclérose Latérale Amyotrophique, Association Française contre les Myopathies (AFM), Paris
- Study start
- Mar 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 19 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Other | Procedure: Anconeus Muscle biopsycontrol subjects with muscle biopsy |
| 1 | Other | Procedure: Anconeus Muscle biopsyALS patients with muscle biopsy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
Key exclusion criteria (9 listed)
- Controls:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anconeus Muscle biopsyAnconeus 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. | Procedure or surgery | 1, 2 |
Primary outcome
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)
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gaelle Bruneteau, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anconeus Muscle biopsy in people with Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2012.