Humanitarian Device Exemption Post-Approval Study of NeuRx Diaphragm Pacing System for Amyotrophic Lateral Sclerosis

This study is currently recruiting participants.
Verified August 2012 by Synapse Biomedical
Sponsor:
Information provided by (Responsible Party):
Synapse Biomedical
ClinicalTrials.gov Identifier:
NCT01605006
First received: May 22, 2012
Last updated: August 24, 2012
Last verified: August 2012
  Purpose

This post-approval study will follow 60 participants who have ALS, documented chronic hypoventilation, and bilateral phrenic nerve function, and who undergo the surgical implantation procedure to receive the NeuRx Diaphragm Pacing System device. Participants who are successfully implanted with the device will use it for daily diaphragm conditioning sessions. Participants will be followed for at least two years (until the last enrolled participant reaches the 2-year follow-up visit). Safety and probable benefit outcome measures will be assessed.


Condition Intervention
Amyotrophic Lateral Sclerosis (ALS)
Device: NeuRx Diaphragm Pacing System (DPS)

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HDE Post-Approval Study (PAS) of NeuRx DPS for ALS

Resource links provided by NLM:


Further study details as provided by Synapse Biomedical:

Primary Outcome Measures:
  • Safety Outcome Measure -- Occurrence of major device-related (including procedure-related) adverse events as defined below. [ Time Frame: follow-up assessments at 3-month intervals ] [ Designated as safety issue: Yes ]
    • Serious capnothorax requiring invasive intervention
    • Mechanical ventilation for 24 hours or longer post-procedure
    • Post-procedure extubation failure resulting in permanent tracheostomy ventilation
    • Perioperative complication which delays initiation of NeuRx DPS therapy
    • Severe discomfort due to stimulation which is unable to be tolerated or resolved
    • Device malfunction which interrupts or causes an undesired diminution of NeuRx DPS therapy
    • Electrode dislodgement from the diaphragm
    • Wire infection
    • Any other device- or procedure-related serious adverse event


Secondary Outcome Measures:
  • Probable Benefit Outcome Measure [ Time Frame: follow-up assessments at 3-month intervals ] [ Designated as safety issue: No ]
    Survival, defined as time to (a) death or (b) permanent tracheostomy mechanical ventilation (PTV) with discontinuation of pacing. (All deaths and PTV events will be reported regardless of relationship to the device or procedure.)


Estimated Enrollment: 60
Study Start Date: July 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
NeuRx DPS On-Label Treatment
All study participants who meet the study eligibility criteria will undergo the surgical implantation procedure to receive the NeuRx DPS. Participants who are successfully implanted with the electrodes will use the NeuRx DPS system for diaphragm conditioning.
Device: NeuRx Diaphragm Pacing System (DPS)
The NeuRx DPS is a percutaneous, intramuscular, diaphragm stimulation system which is implanted using standard laparoscopic surgical techniques in an outpatient procedure. The implanted intramuscular diaphragm electrodes are connected to a four channel external stimulator at a percutaneous exit site. DPS is designed to help ALS patients breathe by providing conditioning stimulation of the diaphragm muscles. Recommended frequency of diaphragm conditioning is at least 3 times per day with each session lasting at least 30 minutes. Patients may find it helpful to use the DPS for longer periods to help with breathing. DPS may be used at the same time as non-invasive ventilation. Patents may also sleep with the DPS to assist with breathing difficulties at night.
Other Names:
  • diaphragm pacing
  • diaphragmatic pacing
  • phrenic nerve stimulation

Detailed Description:

This is a prospective, non-randomized, open-label, interventional, post-approval (FDA) study of the NeuRx Diaphragm Pacing System (DPS) device. The study will enroll 60 participants who have amyotrophic lateral sclerosis (ALS), meet the FDA-approved device indications for use, and undergo the surgical implantation procedure to receive the device. The device is intended for use in ALS patients with a stimulatable diaphragm (both right and left portions) as demonstrated by voluntary contraction or phrenic nerve conduction studies, and who are experiencing chronic hypoventilation (CH), but not progressed to an FVC less than 45% predicted. Participants who are successfully implanted with the device will use it for daily diaphragm conditioning sessions. Participants will be followed for at least two years (until the last enrolled participant reaches the 2-year follow-up visit). Safety and probable benefit outcome measures will be assessed. The primary objective of the study is: (1) (Safety) Characterize the types and frequency of major device-related adverse events (AEs) over the time of device use. Secondary objectives of the study are: (2) (Safety) Determine whether the frequency of major device-related AEs increases dramatically toward end of life; and (3) (Probable Benefit) Determine whether there is a relationship between survival time and onset type (bulbar and limb), time from onset to treatment, and use of NIV, riluzole, or PEG in patients treated with the device.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 21 or older.
  2. Participants with familial or sporadic ALS diagnosed as laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria.
  3. Bilateral phrenic nerve function clinically acceptable as demonstrated by bilateral diaphragm movement with fluoroscopic sniff test or with EMG recordings and nerve conduction times.
  4. Chronic hypoventilation was documented by at least one of the following:

    • FVC less than 50% predicted, or
    • /MIP/ less than 60 cmH2O, or
    • PaCO2 greater than or equal to 45 mmHg, or
    • Nocturnal SaO2 less than or equal to 88% for at least five continuous minutes
  5. Suitable surgical candidate.
  6. Negative pregnancy test in female participants of childbearing potential.
  7. Informed consent from patient or designated representative.

Exclusion Criteria:

  1. Underlying cardiac or pulmonary disease that would increase the risk of general anesthesia.
  2. Underlying pulmonary diseases that were present prior to ALS that would affect pulmonary tests independent of ALS.
  3. Uncontrolled excessive secretions.
  4. FVC less than 45% predicted at time of surgery.
  5. Preexisting implanted electrical device such as pacemaker or cardiac defibrillator.
  6. Pre-existing diaphragm abnormality such as a hiatal hernia or paraesophageal hernia of abdominal contents going into the thoracic cavity.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01605006

Contacts
Contact: Michael Fritz 888-767-3770 ext 134 mfritz@synapsebiomedical.com

Locations
United States, California
California Pacific Medical Center -- Forbes Norris MDA/ALS Research Center Recruiting
San Francisco, California, United States, 94115
Contact: Robert G. Miller, M.D.    415-600-3604    MillerRX@cpmcri.org   
Principal Investigator: Robert G. Miller, M.D.         
Sponsors and Collaborators
Synapse Biomedical
Investigators
Principal Investigator: Robert G. Miller, M.D. Forbes Norris MDA/ALS Research Center, California Pacific Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Synapse Biomedical
ClinicalTrials.gov Identifier: NCT01605006     History of Changes
Other Study ID Numbers: CLIN 20-0009-0020
Study First Received: May 22, 2012
Last Updated: August 24, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Synapse Biomedical:
amyotrophic lateral sclerosis
ALS
motor neuron disease
diaphragm
diaphragm pacing
diaphragmatic pacing
phrenic pacing
phrenic nerve
phrenic nerve stimulation
NeuRx DPS
DPS
chronic hypoventilation
respiration
ventilation
breathing
Humanitarian Device Exemption
HDE
post-approval study

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

ClinicalTrials.gov processed this record on April 21, 2014