Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation (RespiStimALS)

December 21, 2015 updated by: Assistance Publique - Hôpitaux de Paris

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 3

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, 75013
        • APHP, GH Pitié Salpêtrière

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: phenic nerve stimulation
effective phenic nerve stimulation NeurX™ (Synapse Biomedical)
Device: phenique nerve stimulation NeurX™ (Synapse Biomedical)
phenique nerve stimulation NeurX™ (Synapse Biomedical)
Sham Comparator: sham
sham phenic nerve stimulation
Device: sham phrenic nerve stimulation
sham phenic nerve stimulation
Other Names:
  • sham phenic nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Survival without NIV 2 years after the phrenic nerve implantation.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
global survival from onset disease
Time Frame: 2 years
2 years
effects on sleep
Time Frame: 24 months
24 months
Quality of life and daily activities
Time Frame: 24 months
24 months

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

ARSla (Association pour la recherche sur la SLA)
Fondation Thierry Latran

Investigators

  • Principal Investigator: Gonzalez-Bermejo Jesus, Md, PhD, APHP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2012

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

April 20, 2012

First Submitted That Met QC Criteria

April 20, 2012

First Posted (Estimate)

April 23, 2012

Study Record Updates

Last Update Posted (Estimate)

December 22, 2015

Last Update Submitted That Met QC Criteria

December 21, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOM11046

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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