Multi-center, randomized controlled study of the NeuRx(RegisteredTM) Diaphragm Pacing System[?] in participants with Amyotrophic Lateral Sclerosis (ALS)
The primary objective of the study is to compare standard of care (control) to DPS with respect to survival.
Survival is the primary outcome measure. Death or requirement of permanent, invasive mechanical ventilation with tracheostomy or endotracheal tube will be equivalent survival end points (Bensimon 1994). in this study of a surgically implanted device, it is important to use an objective primary outcome measure as it is not feasible to mask subjects to DPS treatment that requires general anesthesia and an invasive surgical procedure. in addition, the potential risks associated with surgery and generalized anesthesia for an aLS subject would not ethically warrant the use of a sham surgical control.
The study is a randomized controlled study to compare standard of care (control) to DPS (diaphragm stimulator named The neuRx[RegisteredTM] Diaphragm Pacing System[TM]). 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). With HDe approval, aLS subjects may receive DPS outside of the proposed clinical trial. 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.
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:
a) Maximal static inspiratory pressure (MIP) <60 cm H20.
b) Upright or supine forced vital capacity (FVC) <50% predicted for gender, age, and height.
4) Both hemi-diaphragms must be able to be stimulated with a recordable compound muscle action potential (CMAP >= 0.1milivolts amplitude and distal latency <= 11 milliseconds) with standard phrenic nerve conduction studies.
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-naive 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.