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Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation (RespiStimALS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborators:
ARSla (Association pour la recherche sur la SLA)
Fondation Thierry Latran
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01583088
First received: April 20, 2012
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Respiratory Insufficiency
Device: phenique nerve stimulation NeurX™ (Synapse Biomedical)
Device: sham phrenic nerve stimulation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Can Diaphragm Pacing Delay Non Invasive Ventilation in Amyotrophic Lateral Sclerosis ? a Randomized Controlled Study

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Survival without NIV 2 years after the phrenic nerve implantation. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • global survival from onset disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • effects on sleep [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Quality of life and daily activities [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: September 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: phenic nerve stimulation
effective phenic nerve stimulation NeurX™ (Synapse Biomedical)
Device: phenique nerve stimulation NeurX™ (Synapse Biomedical)
phenique nerve stimulation NeurX™ (Synapse Biomedical)
Other Name: phenique nerve stimulation NeurX™ (Synapse Biomedical)
Sham Comparator: sham
sham phenic nerve stimulation
Device: sham phrenic nerve stimulation
sham phenic nerve stimulation
Other Name: sham phenic nerve 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01583088

Contacts
Contact: Gonzalez-Bermejo Jesus, MD, PhD +33 (0) 1 42167859 jesus.gonzalez@psl.aphp.fr

Locations
France
APHP, GH Pitié Salpêtrière Recruiting
Paris, France, 75013
Contact: Gonzalez-Bermejo Jesus, MD, PhD    +33 (0) 1 42167859    jesus.gonzalez@psl.aphp.fr   
Principal Investigator: Gonzalez-Bermejo Jesus, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
ARSla (Association pour la recherche sur la SLA)
Fondation Thierry Latran
Investigators
Principal Investigator: Gonzalez-Bermejo Jesus, Md, PhD APHP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01583088     History of Changes
Other Study ID Numbers: AOM11046
Study First Received: April 20, 2012
Last Updated: June 13, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Amyotrophic lateral sclerosis,
Diaphragm
Mechanical ventilation
Phrenic nerve stimulation
Respiratory insufficiency

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Respiratory Insufficiency
Sclerosis
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Respiration Disorders
Respiratory Tract Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies

ClinicalTrials.gov processed this record on November 20, 2014