Amyotrophic Lateral SclerosisPhase 3RespiStimALSNCT01583088
Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
A Phase 3 study testing phenique nerve stimulation NeurX™ (Synapse Biomedical) in people with Amyotrophic Lateral Sclerosis and Respiratory Insufficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
ALS is is characterized by a progressive degeneration of motor neurons, leading to progressive weakness of muscles, including respiratory muscles, the diaphragm. Although specific therapy is lacking, correct respiratory therapy improves quality of life and increases survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Respiratory Insufficiency
- What is being tested?
- phenique nerve stimulation NeurX™ (Synapse Biomedical)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2012to Nov 2015
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis is laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria
- Forced Vital Capacity (FVC) from 80 - 60% of predicted values at enrollment
- Bilateral phrenic nerve function acceptable as demonstrated by bilateral diaphragm EMG recordings and nerve conduction times without axonal lesion
Who cannot join
- Active cardiovascular disease that would increase the risk of general anesthesia. (FEVG<60%)
- Underlying pulmonary diseases that were present prior to ALS that would effect pulmonary tests independent of ALS, in particular COPD with FEV1<30%
- Pre-existing implanted electrical device such as a pacemaker or cardiac defibrillator
- respiratory infection or decompensation in the last 30 days
- Marked obesity affecting suitability for surgery
- Significant scoliosis or chest deformity affecting suitability for surgery
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- Pre-existing diaphragm abnormality such as a hiatal hernia or paraesophageal hernia
- Patient on NIV, CPAP or Oxygen for a reason other than ALS
- Criteria for NIV (VC<50% of predicted values and/or Pi max and SNIP<60% of predicted values; and/or nocturnal desaturations without SAOS and/or PaCO2>45 mm d'Hg)
- Supine VC<50% of predicted values
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Can Diaphragm Pacing Delay Non Invasive Ventilation in Amyotrophic Lateral Sclerosis ? a Randomized Controlled Study
ALS is is characterized by a progressive degeneration of motor neurons, leading to progressive weakness of muscles, including respiratory muscles, the diaphragm. Although specific therapy is lacking, correct respiratory therapy improves quality of life and increases survival. Substituting the failing respiratory muscles by non invasive mechanical ventilatory assistance (NIV) is the current standard of care. Intradiaphragmatic phrenic nerve stimulation is a new treatment and has been the object of a preliminary international proof-of-concept multicenter trial. This trial suggests that the intradiaphragmatic phrenic nerve stimulation slows down the rate of decline of the diaphragm. Our new hypothesis is that phrenic stimulation induces diaphragm conditioning and can delay the need for mechanical ventilation in ALS patients. We will study, during 24 months, 2 groups of 37 patients at the beginning of the respiratory dysfunction, using a intradiaphragmatic phrenic nerve stimulation in one group and a sham stimulation in the other group. Although, all the patients will be implanted, thus, at the end of the study, all the patients will receive effective stimulation.
Read the detailed description
ALS is is characterized by a progressive degeneration of upper and lower motor neurons, leading to progressive weakness of bulbar, limb, thoracic and abdominal muscles. Although specific therapy is lacking, correct respiratory therapy improves quality of life and increases survival. Substituting the failing respiratory muscles by non invasive mechanical ventilatory assistance (NIV) is the current standard of care.Intradiaphragmatic phrenic nerve stimulation, has been the object of a preliminary proof-of-concept multicenter trial (ClinicalTrials.gov NCT00420719).
Aim of the study : To test the hypothesis that phrenic stimulation induced diaphragm conditioning can delay the need for mechanical ventilation in ALS patients.
Methods : It is a double blind randomized study. Patients presenting with early signs of respiratory impairment (VC between 85 and 60%), but with a preserved electromyographic response of the diaphragm to phrenic nerve stimulation, will be randomized in 2 groups. All the patients will be treated according to current standards of care. They will all be implanted with a phrenic stimulator, and then randomized between actual diaphragm conditioning and sham stimulation.
Respiratory function will be followed up on a trimonthly basis, with polysomnography and diaphragmatic EMG biannually. NIV (+ stimulation for both groups), will be initiated according to currently recommended criteria of hypoventilation.
The main outcome of the study will be the number of months between the phrenic nerve implantation and the introduction of NIV. Currently available data, showing that diaphragm pacing can increase the number of patients without NIV at 2 years from 2,5% to 15% of the patients, requires the enrollment of 37 patients in each group. Secondary end-points will include i.Survival ii. Effects on sleep iii. Quality of life and daily activities
- Being tested
- phenique nerve stimulation NeurX™ (Synapse Biomedical), sham phrenic nerve stimulation
- Keywords
- Amyotrophic lateral sclerosis,, Diaphragm, Mechanical ventilation, Phrenic nerve stimulation, Respiratory insufficiency
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenique nerve stimulation NeurX™ (Synapse Biomedical)Device
phenique nerve stimulation NeurX™ (Synapse Biomedical)
sham phrenic nerve stimulationDevice
Also called sham phenic nerve stimulation
sham phenic nerve stimulation
| Study group | Role | What they receive |
|---|---|---|
| phenic nerve stimulation | Experimental | effective phenic nerve stimulation NeurX™ (Synapse Biomedical) Receives: Device: phenique nerve stimulation NeurX™ (Synapse Biomedical) |
| sham | Sham comparator | sham phenic nerve stimulation Receives: Device: sham phrenic nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without NIV 2 years after the phrenic nerve implantation.
Measured: 2 years
Secondary outcomes (3)
global survival from onset disease
Measured: 2 years
effects on sleep
Measured: 24 months
Quality of life and daily activities
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2012 (estimated)
- Study startSep 2012
- Primary completionNov 2015
- Study completionNov 2015
Why it stopped: in the absence of benefits and because of a statistically significant excess mortality in the group of patients receiving active stimulation.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- ARSla (Association pour la recherche sur la SLA), Fondation Thierry Latran
- Responsible party
- Sponsor
- Investigators
- Gonzalez-Bermejo Jesus, Md, PhD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01583088
- Sponsor's protocol ID
- AOM11046
- Acronym
- RespiStimALS
- Status last verified
- Apr 2015
- First submitted
- 20 Apr 2012
- Last updated
- 22 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Guimaraes-Costa R, Similowski T, Rivals I, Morelot-Panzini C, Nierat MC, Bui MT, Akbar D, Straus C, Romero NB, Michel PP, Menegaux F, Salachas F, Gonzalez-Bermejo J, Bruneteau G; RespiStimALS team; contributors to the RespiStimALS study were:. Human diaphragm atrophy in amyotrophic lateral sclerosis is not predicted by routine respiratory measures. Eur Respir J. 2019 Feb 14;53(2):1801749. doi: 10.1183/13993003.01749-2018. Print 2019 Feb.
PubMed 30523161Gonzalez-Bermejo J, Morelot-Panzini C, Tanguy ML, Meininger V, Pradat PF, Lenglet T, Bruneteau G, Forestier NL, Couratier P, Guy N, Desnuelle C, Prigent H, Perrin C, Attali V, Fargeot C, Nierat MC, Royer C, Menegaux F, Salachas F, Similowski T. Early diaphragm pacing in patients with amyotrophic lateral sclerosis (RespiStimALS): a randomised controlled triple-blind trial. Lancet Neurol. 2016 Nov;15(12):1217-1227. doi: 10.1016/S1474-4422(16)30233-2. Epub 2016 Oct 11.
PubMed 27751553
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Diaphragm Pacing Delay Non Invasive Ventilation in Amyotrophic Lateral Sclerosis ? a Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT01583088
- Acronym / sponsor ID
- RespiStimALS / AOM11046
- Keywords
- Amyotrophic lateral sclerosis,, Diaphragm, Mechanical ventilation, Phrenic nerve stimulation, Respiratory insufficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: in the absence of benefits and because of a statistically significant excess mortality in the group of patients receiving active stimulation.
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- ARSla (Association pour la recherche sur la SLA), Fondation Thierry Latran
- Study start
- Sep 2012
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 23 Apr 2012 (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.
ALS is is characterized by a progressive degeneration of motor neurons, leading to progressive weakness of muscles, including respiratory muscles, the diaphragm. Although specific therapy is lacking, correct respiratory therapy improves quality of life and increases survival. Substituting the failing respiratory muscles by non invasive mechanical ventilatory assistance (NIV) is the current standard of care. Intradiaphragmatic phrenic nerve stimulation is a new treatment and has been the object of a preliminary international proof-of-concept multicenter trial. This trial suggests that the intradiaphragmatic phrenic nerve stimulation slows down the rate of decline of the diaphragm. Our new hypothesis is that phrenic stimulation induces diaphragm conditioning and can delay the need for mechanical ventilation in ALS patients. We will study, during 24 months, 2 groups of 37 patients at the beginning of the respiratory dysfunction, using a intradiaphragmatic phrenic nerve stimulation in one group and a sham stimulation in the other group. Although, all the patients will be implanted, thus, at the end of the study, all the patients will receive effective stimulation.
Detailed description
ALS is is characterized by a progressive degeneration of upper and lower motor neurons, leading to progressive weakness of bulbar, limb, thoracic and abdominal muscles. Although specific therapy is lacking, correct respiratory therapy improves quality of life and increases survival. Substituting the failing respiratory muscles by non invasive mechanical ventilatory assistance (NIV) is the current standard of care.Intradiaphragmatic phrenic nerve stimulation, has been the object of a preliminary proof-of-concept multicenter trial (ClinicalTrials.gov NCT00420719).
Aim of the study : To test the hypothesis that phrenic stimulation induced diaphragm conditioning can delay the need for mechanical ventilation in ALS patients.
Methods : It is a double blind randomized study. Patients presenting with early signs of respiratory impairment (VC between 85 and 60%), but with a preserved electromyographic response of the diaphragm to phrenic nerve stimulation, will be randomized in 2 groups. All the patients will be treated according to current standards of care. They will all be implanted with a phrenic stimulator, and then randomized between actual diaphragm conditioning and sham stimulation.
Respiratory function will be followed up on a trimonthly basis, with polysomnography and diaphragmatic EMG biannually. NIV (+ stimulation for both groups), will be initiated according to currently recommended criteria of hypoventilation.
The main outcome of the study will be the number of months between the phrenic nerve implantation and the introduction of NIV. Currently available data, showing that diaphragm pacing can increase the number of patients without NIV at 2 years from 2,5% to 15% of the patients, requires the enrollment of 37 patients in each group. Secondary end-points will include i.Survival ii. Effects on sleep iii. Quality of life and daily activities
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| phenic nerve stimulation | Experimental | Device: phenique nerve stimulation NeurX™ (Synapse Biomedical)effective phenic nerve stimulation NeurX™ (Synapse Biomedical) |
| sham | Sham comparator | Device: sham phrenic nerve stimulationsham phenic nerve stimulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis is laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria
- Forced Vital Capacity (FVC) from 80 - 60% of predicted values at enrollment
- Bilateral phrenic nerve function acceptable as demonstrated by bilateral diaphragm EMG recordings and nerve conduction times without axonal lesion
Key exclusion criteria (10 listed)
- Active cardiovascular disease that would increase the risk of general anesthesia. (FEVG<60%)
- Underlying pulmonary diseases that were present prior to ALS that would effect pulmonary tests independent of ALS, in particular COPD with FEV1<30%
- Pre-existing implanted electrical device such as a pacemaker or cardiac defibrillator
- respiratory infection or decompensation in the last 30 days
- Marked obesity affecting suitability for surgery
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 |
|---|---|---|
| phenique nerve stimulation NeurX™ (Synapse Biomedical)phenique nerve stimulation NeurX™ (Synapse Biomedical) | Device | phenic nerve stimulation |
| sham phrenic nerve stimulationAlso: sham phenic nerve stimulationsham phenic nerve stimulation | Device | sham |
Primary outcome
Survival without NIV 2 years after the phrenic nerve implantation.
Time frame: 2 years
3 secondary outcomes
global survival from onset disease
Time frame: 2 years
effects on sleep
Time frame: 24 months
Quality of life and daily activities
Time frame: 24 months
Results and safety
The study was stopped early (reason given: in the absence of benefits and because of a statistically significant excess mortality in the group of patients receiving active stimulation.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2015.
- Derived from this study: PubMed 30523161Guimaraes-Costa R, Similowski T, Rivals I, Morelot-Panzini C, Nierat MC, Bui MT, Akbar D, Straus C, Romero NB, Michel PP, Menegaux F, Salachas F, Gonzalez-Bermejo J, Bruneteau G; RespiStimALS team; contributors to the RespiStimALS study were:. Human diaphragm atrophy in amyotrophic lateral sclerosis is not predicted by routine respiratory measures. Eur Respir J. 2019 Feb 14;53(2):1801749. doi: 10.1183/13993003.01749-2018. Print 2019 Feb.
- Derived from this study: PubMed 27751553Gonzalez-Bermejo J, Morelot-Panzini C, Tanguy ML, Meininger V, Pradat PF, Lenglet T, Bruneteau G, Forestier NL, Couratier P, Guy N, Desnuelle C, Prigent H, Perrin C, Attali V, Fargeot C, Nierat MC, Royer C, Menegaux F, Salachas F, Similowski T. Early diaphragm pacing in patients with amyotrophic lateral sclerosis (RespiStimALS): a randomised controlled triple-blind trial. Lancet Neurol. 2016 Nov;15(12):1217-1227. doi: 10.1016/S1474-4422(16)30233-2. Epub 2016 Oct 11.
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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.
Gonzalez-Bermejo Jesus, Md, PhD principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing phenique nerve stimulation NeurX™ (Synapse Biomedical) in people with Amyotrophic Lateral Sclerosis and Respiratory Insufficiency, 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 3 inclusion and 10 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: stopped early, as of the sponsor's last update on 22 Dec 2015. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: in the absence of benefits and because of a statistically significant excess mortality in the group of patients receiving active stimulation.). Results are not available in the source record.
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?
Survival without NIV 2 years after the phrenic nerve implantation. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01583088, which also lists 2 linked publications.
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 22 Dec 2015.