Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation

NCT01583088 | Terminated Phase 3 DMC

• 1 other identifier: AOM11046
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Amyotrophic Lateral Sclerosis; Respiratory Insufficiency

Keywords

Amyotrophic lateral sclerosis,; Diaphragm; Mechanical ventilation; Phrenic nerve stimulation; Respiratory insufficiency

Outcome Measures

Primary Outcomes (1)

• Survival without NIV 2 years after the phrenic nerve implantation.

  2 years

Secondary Outcomes (3)

• global survival from onset disease

  2 years

• effects on sleep

  24 months

• Quality of life and daily activities

  24 months

Study Arms (2)

phenic nerve stimulation

EXPERIMENTAL

effective phenic nerve stimulation NeurX™ (Synapse Biomedical)

Device: phenique nerve stimulation NeurX™ (Synapse Biomedical)

sham

SHAM COMPARATOR

sham phenic nerve stimulation

Device: sham phrenic nerve stimulation

Interventions

phenique nerve stimulation NeurX™ (Synapse Biomedical) DEVICE

phenique nerve stimulation NeurX™ (Synapse Biomedical)

phenic nerve stimulation

sham phrenic nerve stimulation DEVICE

sham phenic nerve stimulation

Also known as: sham phenic nerve stimulation

sham

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• ARSla (Association pour la recherche sur la SLA): collaborator
• Fondation Thierry Latran: collaborator

Study Sites (1)

APHP, GH Pitié Salpêtrière

Paris, 75013, France

Location

Related Publications (2)

• 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.

  PMID: 30523161 DERIVED

• Gonzalez-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.

  PMID: 27751553 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Gonzalez-Bermejo Jesus, Md, PhD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2012
• First Posted: April 23, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 22, 2015

Record last verified: 2015-04

Locations

FR (1)