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

Not Applicable
Completed
Conditions
Amyotrophic Lateral Sclerosis (ALS)
Interventions
Device: NeuRx Diaphragm Pacing System (DPS)
Registration Number
NCT01605006
Lead Sponsor
Synapse Biomedical
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
97
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
NeuRx Diaphragm Pacing System (DPS)NeuRx Diaphragm Pacing System (DPS)Surgical implantation of the NeuRx DPS (on label use).
Primary Outcome Measures
NameTimeMethod
Safety Outcome Measure -- Occurrence of major device-related (including procedure-related) adverse events as defined below.follow-up assessments at 3-month intervals

* 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
NameTimeMethod
Probable Benefit Outcome Measurefollow-up assessments at 3-month intervals

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.)

Trial Locations

Locations (11)

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Mayo Clinic

🇺🇸

Jacksonville, Florida, United States

California Pacific Medical Center -- Forbes Norris MDA/ALS Research Center

🇺🇸

San Francisco, California, United States

University of Colorado Denver

🇺🇸

Denver, Colorado, United States

Duke University

🇺🇸

Durham, North Carolina, United States

University Hospitals Case Medical Center

🇺🇸

Cleveland, Ohio, United States

Providence St. Vincent Medical Center

🇺🇸

Portland, Oregon, United States

Stony Brook University

🇺🇸

Stony Brook, New York, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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