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

Primary Purpose

Amyotrophic Lateral Sclerosis (ALS)

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
NeuRx Diaphragm Pacing System (DPS)
Sponsored by
Synapse Biomedical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis (ALS) focused on measuring 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

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cedars-Sinai Medical Center
  • California Pacific Medical Center -- Forbes Norris MDA/ALS Research Center
  • University of Colorado Denver
  • Mayo Clinic
  • Northwestern University
  • University of Kansas Medical Center
  • University of Nebraska Medical Center
  • Stony Brook University
  • Duke University
  • University Hospitals Case Medical Center
  • Providence St. Vincent Medical Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

NeuRx Diaphragm Pacing System (DPS)

Arm Description

Surgical implantation of the NeuRx DPS (on label use).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.)

Full Information

First Posted
May 22, 2012
Last Updated
March 25, 2020
Sponsor
Synapse Biomedical
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1. Study Identification

Unique Protocol Identification Number
NCT01605006
Brief Title
Humanitarian Device Exemption Post-Approval Study of NeuRx Diaphragm Pacing System for Amyotrophic Lateral Sclerosis
Official Title
HDE Post-Approval Study (PAS) of NeuRx DPS for ALS
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
July 2012 (Actual)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
February 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Synapse Biomedical

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis (ALS)
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NeuRx Diaphragm Pacing System (DPS)
Arm Type
Other
Arm Description
Surgical implantation of the NeuRx DPS (on label use).
Intervention Type
Device
Intervention Name(s)
NeuRx Diaphragm Pacing System (DPS)
Other Intervention Name(s)
diaphragm pacing, diaphragmatic pacing, phrenic nerve stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety Outcome Measure -- Occurrence of major device-related (including procedure-related) adverse events as defined below.
Description
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
Time Frame
follow-up assessments at 3-month intervals
Secondary Outcome Measure Information:
Title
Probable Benefit Outcome Measure
Description
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.)
Time Frame
follow-up assessments at 3-month intervals

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 21 or older. Participants with familial or sporadic ALS diagnosed as laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria. Bilateral phrenic nerve function clinically acceptable as demonstrated by bilateral diaphragm movement with fluoroscopic sniff test or with EMG recordings and nerve conduction times. 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 Suitable surgical candidate. Negative pregnancy test in female participants of childbearing potential. Informed consent from patient or designated representative. Exclusion Criteria: Underlying cardiac or pulmonary disease that would increase the risk of general anesthesia. Underlying pulmonary diseases that were present prior to ALS that would affect pulmonary tests independent of ALS. Uncontrolled excessive secretions. FVC less than 45% predicted at time of surgery. Preexisting implanted electrical device such as pacemaker or cardiac defibrillator. Pre-existing diaphragm abnormality such as a hiatal hernia or paraesophageal hernia of abdominal contents going into the thoracic cavity.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert G. Miller, M.D.
Organizational Affiliation
Forbes Norris MDA/ALS Research Center, California Pacific Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
California Pacific Medical Center -- Forbes Norris MDA/ALS Research Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Colorado Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Stony Brook University
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Providence St. Vincent Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.accessdata.fda.gov/cdrh_docs/pdf10/H100006b.pdf
Description
FDA Summary of Safety and Probable Benefit for Humanitarian Device Exemption (Approved September 28, 2011)

Learn more about this trial

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

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