Pilot Placebo-Controlled Study of Early Noninvasive Ventilation for ALS (S43.003)

Objective: The aim of this pilot trial was to evaluate usage and tolerability of both active and sham noninvasive positive pressure ventilation (NIV) in ALS patients with a forced vital capacity (FVC) ≥50[percnt]. Background: Treatment of ALS patients with noninvasive positive pressure ventilation when forced vital capacity <50[percnt] appears to improve ALS patient survival and quality of life and is supported by guideline statements. Improved survival may be explained by slower rate of pulmonary function decline. Initiation of NIV earlier may further attenuate pulmonary function decline and improve survival. However, the tolerability of early NIV in ALS is unknown. Design/Methods: This is a prospective, double-blind, randomized, placebo-controlled pilot study. Fifty-four subjects with ALS whose FVC ≥50[percnt] and with no prior use of NIV were randomized to receive either sham (n=26) or active (n=28) NIV. Subjects had active surveillance until they reached an FVC <50[percnt] or became symptomatic. Results: No difference (p=0.097) in average NIV use per day was identified between the sham (2.0 hours (95[percnt] CI: 1.1, 3.0)) and active (3.3 hours (95[percnt] CI: 2.0, 4.6)) NIV groups. Subjects perception of treatment assignment did not differ by treatment group (p=0.3). The majority of sham NIV (88[percnt]) and active NIV (73[percnt]) subjects reported mild or no problems with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p=0.049). Survival and changes in maximum expiratory pressure and mean inspiratory pressure did not differ between treatment groups. Conclusions: Sham-NIV is a feasible placebo for clinical trials of early NIV therapy in ALS. The trend toward improved respiratory function seen in this pilot trial warrants further study of early NIV therapy in ALS. Study supported by: NIH K23NS055200, U10NS086526 Disclosure: Dr. Jacobs has nothing to disclose. Dr. Baek has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Migda has nothing to disclose. Dr. Funckes has nothing to disclose. Dr. Gruis has received personal compensation from Alnylam Pharmaceuticals.