Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation

Amyotrophic Lateral Sclerosis Clinical Trial

— RespiStimALS  

Official title:

Can Diaphragm Pacing Delay Non Invasive Ventilation in Amyotrophic Lateral Sclerosis ? a Randomized Controlled Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01583088
• Other study ID #: AOM11046
• Status: Terminated
• Phase: Phase 3
• First received: April 20, 2012
• Last updated: December 21, 2015
• Start date: September 2012
• Est. completion date: November 2015

Study information

• Verified date: April 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical 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. 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 74
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Pulmonary Valve Insufficiency
• Respiratory Insufficiency
• Sclerosis

Intervention

Device:
• phenique nerve stimulation NeurX™ (Synapse Biomedical)
phenique nerve stimulation NeurX™ (Synapse Biomedical)
• sham phrenic nerve stimulation
sham phenic nerve stimulation

Locations

Country	Name	City	State
France	APHP, GH Pitié Salpêtrière	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	ARSla (Association pour la recherche sur la SLA), Fondation Thierry Latran

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival without NIV 2 years after the phrenic nerve implantation.		2 years	Yes
Secondary	global survival from onset disease		2 years	No
Secondary	effects on sleep		24 months	No
Secondary	Quality of life and daily activities		24 months	No