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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Device: NeuRx Diaphragm Pacing System (DPS)	Not Applicable

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	97 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	HDE Post-Approval Study (PAS) of NeuRx DPS for ALS
Study Start Date :	July 2012
Estimated Primary Completion Date :	September 2017
Estimated Study Completion Date :	September 2017

Arms and Interventions

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Arm

Intervention/treatment

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

Outcome Measures

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Primary Outcome Measures :

1. 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 ]
   • 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 :

1. Probable Benefit Outcome Measure [ Time Frame: follow-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.)

Eligibility Criteria

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Ages Eligible for Study:	21 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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Locations

United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
California Pacific Medical Center -- Forbes Norris MDA/ALS Research Center
San Francisco, California, United States, 94115
United States, Colorado
University of Colorado Denver
Denver, Colorado, United States, 80045
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New York
Stony Brook University
Stony Brook, New York, United States, 11794
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Oregon
Providence St. Vincent Medical Center
Portland, Oregon, United States, 97213

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

FDA Summary of Safety and Probable Benefit for Humanitarian Device Exemption (Approved September 28, 2011) 

Responsible Party:	Synapse Biomedical
ClinicalTrials.gov Identifier:	NCT01605006 History of Changes
Other Study ID Numbers:	CLIN 20-0009-0020
First Posted:	May 24, 2012
Last Update Posted:	April 13, 2016
Last Verified:	April 2016

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:

Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases	Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases