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

HDE Post-Approval Study (PAS) of NeuRx DPS for ALS

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Device: NeuRx Diaphragm Pacing System (DPS)

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 Type: Interventional
• Enrollment (Actual): 97
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: NeuRx Diaphragm Pacing System (DPS); Surgical implantation of the NeuRx DPS (on label use).

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome Measure -- Occurrence of major device-related (including procedure-related) adverse events as defined below.	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	follow-up assessments at 3-month intervals

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probable Benefit Outcome Measure	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.)	follow-up assessments at 3-month intervals

Collaborators and Investigators

• Sponsor: Synapse Biomedical
• Investigators: Principal Investigator: Robert G. Miller, M.D., Forbes Norris MDA/ALS Research Center, California Pacific Medical Center

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: May 22, 2012
• First Submitted That Met QC Criteria: May 23, 2012
• First Posted (Estimate): May 24, 2012

Study Record Updates

• Last Update Posted (Actual): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: ALS; breathing; ventilation; amyotrophic lateral sclerosis; motor neuron disease; phrenic nerve; respiration; diaphragm; diaphragm pacing; diaphragmatic pacing; phrenic pacing; phrenic nerve stimulation; NeuRx DPS; DPS; chronic hypoventilation; Humanitarian Device Exemption; HDE; post-approval study
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: CLIN 20-0009-0020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No