Respiratory muscle training in late-onset Pompe disease: Results of a sham-controlled clinical trial

Abstract

To address progressive respiratory muscle weakness in late-onset Pompe disease (LOPD), we developed a 12-week respiratory muscle training (RMT) program. In this exploratory, double-blind, randomized control trial, 22 adults with LOPD were randomized to RMT or sham-RMT. The primary outcome was maximum inspiratory pressure (MIP). Secondary and exploratory outcomes included maximum expiratory pressure (MEP), peak cough flow, diaphragm ultrasound, polysomnography, patient-reported outcomes, and measures of gross motor function. MIP increased 7.6 cmH2O (15.9) in the treatment group and 2.7 cmH2O (7.6) in the control group (P = 0.4670). MEP increased 14.0 cmH2O (25.9) in the treatment group and 0.0 cmH2O (12.0) in the control group (P = 0.1854). The only statistically significant differences in secondary/exploratory outcomes were improvements in time to climb 4 steps (P = 0.0346) and daytime sleepiness (P = 0.0160). The magnitude of changes in MIP and MEP in the treatment group were consistent with our pilot findings but did not achieve statistical significance in comparison to controls. Explanations for this include inadequate power and baseline differences in subject characteristics between groups. Additionally, control group subjects appeared to exhibit an active response to sham-RMT and therefore sham-RMT may not be an optimal control condition for RMT in LOPD.

Keywords: Late-onset Pompe disease; Maximum expiratory pressure; Maximum inspiratory pressure; Pompe disease; Randomized control trial; Respiratory muscle training.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LEC, PSK, LHW, and HNJ have received research/grant support and honoraria from Sanofi Genzyme Corporation. LEC is a member of the Pompe Registry Board of Advisors for Sanofi Genzyme. PSK has received research/grant support, honoraria, and/or consulting fees from Valerion Therapeutics, Amicus Therapeutics, Vertex Pharmaceuticals, and Asklepios BioPharmaceuticals, Inc; is a member of the Pompe and Gaucher Disease Registry Advisory Board for Sanofi Genzyme, Amicus Therapeutics, and Baebies; and has equity in Actus Therapeutics. HNJ has US Patent applications for respiratory muscle training-related intellectual property licensed by Aspire LLC and is a paid consultant for Aspire LLC. LHW receives consulting fees from Wiley Publishing for work as an Associate Editor of Muscle and Nerve. MK, KDC, MTB, JAM, and RMK have no conflicts of interest to report.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Figure 1.. Study Overview.

PSG = polysomnography, RMT Tx = on-site RMT or sham therapy visits, Phone Check = telephone contact with RMT clinician.

Figure 2.

Pretest to posttest change in primary and secondary outcomes. Data are presented as mean (SD). MIP=maximum inspiratory pressure; MEP=maximum expiratory pressure; GSGC=Gait, Stairs, Gowers, Chair; 6MWT=6-minute walk test; R-PACT=Rausch-built Pompe-specific Activity Scale.