Inspiratory Muscle Training in Nemaline Myopathy
Condition: Nemaline Myopathy; Inspiratory Muscle Training
MeSH terms: Muscular Diseases; Myopathies, Nemaline; Respiratory Aspiration
Study type: Interventional

Summary: 
      Nemaline myopathy is a rare congenital myopathy. Respiratory failure is the main cause of
      death in these patients. The primary objective of this study is to determine the effect of a
      8-week inspiratory muscle training program on respiratory muscle function in nemaline
      myopathy patients. The secondary objective is to determine respiratory muscle function in
      nemaline myopathy patients and its correlation with clinical severity and general
      neuromuscular function. The nemaline myopathy patients will be included in the first phase
      for a clinical characterization. From this phase patients will be selected for the second
      phase, which is a controlled before-after trial of inspiratory muscle training. The primary
      outcome is the change in maximal inspiratory pressure (MIP) after active inspiratory muscle
      training
    

Detailed description: 
      Rationale: Nemaline myopathy is a group of congenital, hereditary neuromuscular disorders
      with variable symptoms such as muscle weakness, swallowing dysfunction, and dysarthria.
      Respiratory failure is the main cause of death in nemaline myopathy and occurs even in
      ambulant patients who otherwise appear to be only mildly affected; respiratory muscle
      weakness may even be the presenting feature. Inspiratory muscle training has shown to
      increase inspiratory muscle strength in patients with other neuromuscular disorders. It is
      hypothesized that inspiratory muscle training improves respiratory muscle function in
      nemaline myopathy patients with respiratory muscle weakness.

      Objective: The primary objective is to determine the effect of a 8-week inspiratory muscle
      training program on respiratory muscle function in nemaline myopathy patients. The secondary
      objective is to determine respiratory muscle function in nemaline myopathy patients and its
      correlation with clinical severity and general neuromuscular function.

      Study design: The study consist of two phases. Phase 1: A screening phase with an open design
      from which patients will be selected for the second phase. Phase 2: A controlled before-after
      trial of inspiratory muscle training. The 2 conditions tested are sham IMT and active IMT.

      Study population: Nemaline myopathy patients from the local neuromuscular database will be
      recruited. Furthermore, other centres in the Netherlands will be contacted to expand the
      database of nemaline myopathy patients. Phase 2 requires 23 patients.

      Intervention: Active IMT consists of 15 minutes of IMT, twice a day, 5 days per week for 8
      weeks, at a training workload of 30% of MIP using a resistive inspiratory muscle training
      device. Sham IMT consists of similar training regime using a resistive inspiratory muscle
      training device where the resistance has been removed.

      Main study parameters/endpoints: The primary outcome parameter is the change in maximal
      inspiratory pressure (MIP) after active inspiratory muscle training.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: The intervention of inspiratory muscle training is not associated with any
      risks, but can be challenging in patients with respiratory muscle weakness to perform. There
      will be three visits to the hospital in 16 weeks. The first visit has a maximal duration of 6
      hours (including breaks) and the other two visits 1.5 hour. During these visits several tests
      and physical examinations will be performed. Some of the tests may cause some physical
      discomfort, but none of them carry any risk. Patients may benefit from participating in this
      study by developing improved respiratory muscle function as a result of the inspiratory
      muscle training.
    

Intervention name(s): Threshold IMT, Philips Respironics, Murrysville, PA, USA
Intervention type(s): Device
Intervention description(s): Active inspiratory muscle training (IMT) by the threshold IMT provides consistent and specific pressure for inspiratory muscle strength and endurance training, regardless of how quickly or slowly patients breathe. This device incorporates a flow-independent one-way valve to ensure consistent resistance and features an adjustable specific pressure setting (in cmH20) to be set. When patients inhale through the Threshold IMT, a spring-loaded valve provides a resistance that exercises respiratory muscles through conditioning.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: A controlled before-after trial of inspiratory muscle training will be performed in patients with nemaline myopathy with respiratory muscle weakness. The 2 sequentially tested conditions are sham IMT and active IMT. Patients are not blinded to the conditions, instead patients are instructed that two training methods are tested. First the effect of breathing technique with low resistance (sham IMT) and secondly with high resistance (active IMT).
Masking: None (Open Label)
Primary purpose: Supportive Care