The Muscular Dystrophy Association has committed $750,000 to help support a phase 2 clinical trial assessing the ability of the NeuRx Diaphragm Pacing System (DPS) to improve respiratory function and quality of life in people with amyotrophic lateral sclerosis (ALS).
Developed by Synapse Biomedical in Oberlin, Ohio, the DPS received approval from the U.S. Food and Drug Administration (FDA) on Sept. 29, 2011, as a “humanitarian use device” (HUD) for the treatment of chronic hypoventilation (inadequate breathing) in ALS. The surgically implanted device stimulates the movement of the diaphragm, the main muscle used in breathing.
The FDA gives HUD approval to medical devices intended for use in rare diseases and in which the probable benefits that might be gained from using the device outweigh the risk that it may cause injury or illness. The FDA requires sufficient evidence that HUD devices do not pose "an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use."
To receive the HUD approval, Synapse Biomedical presented the FDA with findings from a multicenter clinical trial in which 86 people with ALS received the DPS for chronic hypoventilation. Trial participants were compared to “matched patient groups” — data on similar patients who had participated in two different published studies, and who had not received the DPS. Synapse Biomedical reports that its study showed use of the NeuRx DPS “with noninvasive ventilation [NIV] could significantly extend their lives and improve sleep quality when compared to NIV use alone.”
Noting that the Synapse trial design was not the “gold standard” for clinical trials, Sanjay Bidichandani, MDA vice president of research, explained that "the DPS is available commercially for humanitarian use, but although Synapse has presented data suggesting the device works, there is no definitive proof that it is effective.”
He said the planned phase 2 clinical trial "is expected to determine whether the DPS can cause significant improvement in respiratory function and improve quality of life for people with ALS."
Respiratory failure is the most common cause of death in ALS.
When the diaphragm muscle weakens, the act of breathing can become conscious and difficult (even though there is nothing wrong with the lungs). Chronic hypoventilation usually requires supportive measures that compensate for weakened muscles by helping move air in and out of the lungs. Standard supportive measures include noninvasive ventilation, which delivers air under pressure via a small, portable machine (bilevel positive airway pressure, or BiPAP, is one example); and invasive ventilation, in which a ventilator delivers air directly into the windpipe through a tracheostomy, or surgically created opening in the neck.
The DPS requires minimally invasive laparoscopic surgery, in which electrodes are surgically implanted in the diaphragm. The device activates the phrenic nerves, which stimulate the diaphragm, supplementing breathing ability and possibly delaying diaphragm shrinkage (atrophy). If the nerves or diaphragm have deteriorated too much, the device is not likely to have any benefit.
In people with ALS who have chronic breathing problems and whose diaphragm still is able to respond to electrical stimulation, the DPS may forestall or negate the need for invasive ventilation.
The device can be used in conjunction with noninvasive ventilation.
The phase 2 trial is expected to enroll 180 people with ALS. Of that number, 120 will receive the DPS, and 60 will receive treatment in line with the current standard of care.
Investigators will compare measures of diaphragm function, dyspnea (shortness of breath) and quality of life between the two groups.
The trial will be conducted at two primary sites: SUNY Upstate Medical University in Syracuse, N.Y., and California Pacific Medical Center in San Francisco (CPMC).
Kirsten Gruis, associate professor of neurology at SUNY, will be the principal investigator for the trial. Jonathan Katz, director of the neuromuscular diseases program at CPMC, will serve as co-principal investigator. Katz also co-directs the MDA/ALS center at that institution.
People with ALS over the age of 21 years with some degree of breathing muscle weakness and hypoventilation, and who meet other criteria, are eligible for participation.
MDA is providing funding for the trial through MDA Venture Philanthropy (MVP), the drug development arm of MDA's translational research program. The ALS Association and Synapse Biomedical also are funding this trial.
For more about the DPS, see A Closer Look: Diaphragm Pacing System (MDA/ALS Newsmagazine, January-March 2012.)
|Editor's note (Aug. 14, 2012):This story was amended to include information about Synapse Biomedical's original trial of the DPS.|