Pilot placebo-controlled trial of early noninvasive ventilation for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an untreatable neurodegenerative disorder characterized by the progressive loss of motor neuron function. Respiratory failure is the most common cause of death in persons with ALS. Treatment of respiratory muscle weakness with nocturnal noninvasive positive pressure ventilation (NIPPV) when forced vital capacity (FVC) is less than 50 percent—but prior to the development of respiratory failure—has prolonged survival in observational studies. Despite the association of NIPPV use and survival, it is unknown whether earlier NIPPV treatment will benefit people with ALS. Also, no placebo‐controlled studies of NIPPV treatment and people with ALS have been conducted. The goals of the this trial are to assess the feasibility of conducting a prospective, randomized, double‐blind, clinical trial of NIPPV versus control (sham) NIPPV in people with ALS who have a FVC greater than 50 percent, and to gain preliminary data on outcome effects. In the trial, the investigators will test the following hypotheses: (1) People with ALS who have a FVC greater than 50 percent can tolerate active NIPPV and control NIPPV, and will find control NIPPV to be a believable treatment; (2) Initiation of active NIPPV in people with ALS who have a FVC greater than 50 percent will have better clinical outcomes with respect to measures of quality of life, rate of pulmonary function decline, and functional outcome; and (3) People with ALS who start active NIPPV early will have improved tolerance later when respiratory weakness has progressed. These aims will enable planning of a subsequent, large‐scale and definitive clinical trial of early NIPPV (FVC greater than 50 percent) in people with ALS. If the benefits of early NIPPV can be confirmed, then a new treatment may be established for this progressive, fatal disease.