Respiratory Muscle Training in Patients With Spinal Muscular Atrophy (SMA).

The aim of this study is to assess the feasibility and efficacy of respiratory muscle training in patients with SMA and respiratory muscle weakness. The hypothesis is that an individualized incremental home-based respiratory muscle training program will be feasible and will improve inspiratory muscle strength, expiratory muscle strength, lung function and patient reported breathing difficulties in patients with SMA.

Study setting: This study is conducted at the outpatient department of the Netherlands SMA center and the Child Development and Exercise Center at the University Medical Center Utrecht (UMCU), The Netherlands. All members of the study team, consisting of physicians, physiotherapists, lung function technicians, clinical exercise physiologists and nurses, have broad experience with SMA due to the national cohort study that is carried out in this center since 2010.

Study design: The RESISTANT study is an investigator-initiated, mono-center study consisting of two parts:

Part 1 (0-4 months): a single blinded randomized sham-controlled trial (RCT). In the first part of the study, the feasibility and efficacy of respiratory muscle training (RMT) in patients with SMA will be determined.

Before the first visit, participants will be recruited for enrollment by a research nurse. Patients who express interest in participating receive a patient information letter and an appointment with the physiotherapist. At the first visit (M0), the physiotherapist further determines whether patients are eligible for participation. After signing the informed consent form, participants are weighed and their length is determined, followed by lung function tests. If the maximum inspiratory mouth pressure (PImax) >80 centimeter of Water Column (cmH2O), participants are excluded for the study. If PImax ≤ 80 cmH2O, participants will be stratified prior to randomization based on PImax (group 1: PImax <60 cmH2O, group 2: PImax ≥60 cmH2O, 60 cmH2O was the median PImax in the group of patients used for the natural history study). Participants will be randomly allocated to the intervention or sham-control group. A variable block randomization method with allocation concealment in a centralized system will be used for randomization. The lung function analyst is blinded for treatment allocation. A data analyst will design and sign the data analysis plan in advance. The data will be analyzed according to the analysis plan by a physiotherapist who is not blinded for treatment allocation. The physiotherapists who will perform the two-weekly telephone calls are not blinded for treatment allocation. Patients will know that there are two treatment groups, and they are informed that it is not yet known which treatment is most effective.