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

• ClinicalTrials.gov Identifier: NCT01605006
• Recruitment Status: Completed
• First Posted: May 24, 2012
• Last Update Posted: March 27, 2020
• Sponsor: Synapse Biomedical
• Information provided by (Responsible Party): Synapse Biomedical

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.

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

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

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

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

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• 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

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

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
• Other Study ID Numbers: CLIN 20-0009-0020
• First Posted: May 24, 2012
• Last Update Posted: March 27, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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:

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