Amyotrophic Lateral Sclerosis (ALS) is an untreatable neurodegenerative disorder characterized by progressive loss of motor neuron function. Respiratory failure is the most common cause of ALS patient death. Treatment of respiratory muscle weakness with nocturnal noninvasive positive pressure ventilation (NIPPV) when forced vital capacity (FVC) is less than 50%, but prior to the development of respiratory failure, has prolonged survival in observational studies. Decline in pulmonary function, measured as rate of FVC decline over time, also appears to be attenuated by NIPPV treatment. Despite the association of NIPPV use and survival, it is unknown whether earlier NIPPV treatment will benefit ALS patients. Additionally, no placebo-controlled studies of NIPPV treatment and ALS patients have been conducted. The goals of the proposed project are to assess the feasibility of performing a prospective, randomized, double-blind, clinical trial of NIPPV versus control (sham) NIPPV in ALS patients with an FVC greater than 50%, and to gain preliminary data on outcome effects. The primary hypotheses to be tested are: 1) ALS patients with an FVC greater than 50% can tolerate active NIPPV and control NIPPV, and will find control NIPPV to be a believable treatment. 2) Initiation of active NIPPV in ALS patients with an FVC greater than 50% will have better clinical outcomes with respect to measures of quality of life, rate of pulmonary function decline, and functional outcome. 3) ALS patients 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%) in patients with ALS. If benefits of early NIPPV can be confirmed, a new treatment would be established for a progressive, lethal disease. The candidate is a neuromuscular fellowship-trained neurologist who is dedicated to a career in patient-oriented ALS research. This application proposes a 5-year career development plan that will include formal training in clinical research design, epidemiology, and biostatistics. The candidate and mentors are committed to the highest quality clinical research endeavors aimed at improving ALS patient care in the United States. The University of Michigan, with a strong Neuromuscular Disorders Center, and School of Public Health will create the perfect environment for this candidate's career development. The proposed research and educational experience will develop the candidate into an independent researcher well prepared to make fundamental contributions to ALS research in the future.
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