Clinical trial NCT01605006: 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
Overall status: COMPLETED
Phase: NA
Conditions: 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
Lead sponsor: Synapse Biomedical
Sponsor class: INDUSTRY
First posted: 2012-05-24
Enrollment: 97
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Safety Outcome Measure -- Occurrence of major device-related (including procedure-related) adverse events as defined below.
timeFrame: follow-up assessments at 3-month intervals
Secondary outcomes:
measure: Probable Benefit Outcome Measure
timeFrame: follow-up assessments at 3-month intervals
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center -- Forbes Norris MDA/ALS Research Center
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
Study officials:
affiliation: Forbes Norris MDA/ALS Research Center, California Pacific Medical Center
name: Robert G. Miller, M.D.
role: PRINCIPAL_INVESTIGATOR
References: