Clinical trial NCT01938495: Diaphragm Pacing System (DPS) In Participants With Amyotrophic Lateral Sclerosis (ALS)
Official title: Multi-Center, Randomized Controlled Study of the NeuRx® Diaphragm Pacing System™ (DPS)In Participants With Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: ALS
DPS
Diaphragm Pacing
Lead sponsor: Barrow Neurological Institute
Sponsor class: OTHER
Collaborators: name: ALS Association
name: Muscular Dystrophy Association
name: Synapse Biomedical
First posted: 2013-09-10
Enrollment: 52
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The study is being conducted to determine if DPS treatment for people with ALS and hypoventilation is associated with improved survival or diaphragm function.

The primary objective of the study is to conduct a multi-center, randomized controlled clinical trial comparing standard of care (control) to diaphragm stimulator treatment with the NeuRx® Diaphragm Pacing System™ (DPS) with respect to survival.

The secondary objective of the study is to conduct a multi-center, randomized controlled clinical trial to compare standard of care treatment (control) to DPS in ALS subjects with hypoventilation.

Detailed description: The study is a randomized controlled study to compare standard of care (control) to DPS (diaphragm stimulator named The NeuRx® Diaphragm Pacing System™). Although it remains uncertain if DPS is efficacious for the ALS subject, given the preliminary studies performed by the device manufacturer, it has received FDA humanitarian device exemption (HDE) approval as a humanitarian use device (HUD). This study will utilize a 2:1 randomization schedule such that eligible ALS subjects will have a 2/3 chance of receiving DPS and 1/3 chance of standard of care (control) treatment.

The NeuRx® Diaphragm Pacing System™ (DPS) is a four channel, implanted percutaneous diaphragm muscle stimulation system. Under general anesthesia, the intramuscular electrodes are laparoscopically implanted in the diaphragm. The ends of the implanted electrodes are tunneled subcutaneously to an exit site on the chest or abdominal wall and connected to an external stimulator.

Eligibility criteria: Inclusion Criteria:

1. Age 21 years or older.
2. Sporadic or familial ALS diagnosed as definite, probable or possible ALS as defined by revised El Escorial criteria.
3. Evidence of hypoventilation at Screening with at least one of the following:

   1. Maximal static inspiratory pressure (MIP) \<60 cm H20.
   2. Upright or supine forced vital capacity (FVC) \<50% predicted for gender, age, and height.
4. A phrenic nerve potential should be recordable bilaterally.
5. Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to randomization (riluzole-naïve subjects are permitted in the study).
6. Capable of providing informed consent and following trial procedures.
7. Geographically accessible to the site.
8. Negative urine pregnancy test at Screening in women of child bearing potential (WOCBP). (Women who are post-menopausal or who have had a hysterectomy are deemed not of child bearing potential).
9. Women of child bearing potential must use an adequate form of contraception: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal (patch or contraceptive ring, for example) contraception), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.

Exclusion Criteria:

1. Upright forced vital capacity (FVC) ≤ 45% of predicted for gender, age, and height.
2. Any prior use of non-invasive ventilation (NIV) outside of sleep (nighttime or naps).
3. Any pulmonary or cardiac disorder or other medical disorder that would be a contraindication for general anesthesia or DPS hardware implantation in the chest.
4. Implanted electrical device such as a pacemaker or cardiac defibrillator.
5. Known diaphragm abnormality such as hiatal hernia or para-esophageal hernia of abdominal contents into the thoracic cavity.
6. Participation in another treatment research study for people with ALS.
7. Exposure to any other agent currently under investigation for the treatment of people with ALS (off-label use or investigational) within 30 days of the Screening Visit.
8. Clinically significant history of unstable or severe cardiac, oncologic, hepatic, psychiatric, renal disease, or other medically significant illness.
9. Pregnant women or women currently breastfeeding.

Primary outcomes:
measure: Survival
timeFrame: Subjects will be assessed on a monthly basis for an 18 month period.
Secondary outcomes:
measure: quality of life
timeFrame: Subjects will be assessed on a monthly basis for an 18 month period.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: California Pacific Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: New Britain
country: United States
facility: Hospital for Special Care
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida, Jacksonville
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health Systems
state: Michigan
city: Saint Louis
country: United States
facility: St Louis University
state: Missouri
city: Lincoln
country: United States
facility: Neurology Associates P.C.
state: Nebraska
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Health Care
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Providence ALS Center
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: San Antonio
country: United States
facility: University of Texas
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Barrow Neurological Institute
name: Jeremy Shefner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: California Pacific Medical Center
name: Jonathan Katz, MD
role: PRINCIPAL_INVESTIGATOR
References: