Stacking Exercises Aid the Decline in FVC and Sick Time
Condition: Duchenne Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Study type: Interventional
Phase: Phase 4

Summary: 
      Duchenne Muscular Dystrophy is complicated by weak breathing muscles and lung infections.
      "Lung volume recruitment" is a technique performed using a face mask or mouthpiece and a
      hand-held resuscitation bag to stack breaths, inflate the lungs and help clear the airways of
      secretions by increasing the forcefulness of a cough. We believe this will slow down the
      steady loss of lung function, prevent lung infection, and improve quality of life. Our aim is
      to compare the outcome of a group of individuals with DMD treated with standard care to
      another group that also receives lung volume recruitment. If effective, this study will
      change clinical practice by including twice-daily treatment as part of the standard of care
      for individuals with DMD, in order to improve their lung health and quality of life.
    

Detailed description: 
      Background: Respiratory complications are the primary cause of morbidity and mortality
      associated with childhood Duchenne Muscular Dystrophy (DMD). Involvement of the respiratory
      muscles leads to progressive hypoventilation and/or recurrent atelectasis and pneumonia
      secondary to decreased cough efficacy. Lung volume recruitment (LVR) is a means of stacking
      breaths to achieve maximal lung inflation (MIC), prevent micro-atelectasis, and improve cough
      efficacy. Although it has been recommended by some experts as the "standard of care" for
      individuals with neuromuscular disease, the strategy has not been widely implemented in DMD
      given the lack of clinical trials to date to support its efficacy as well as the additional
      burden of care required in a population already requiring multiple interventions.

      Primary Objective: To determine whether LVR, in addition to conventional treatment, is
      successful in reducing decline from baseline in forced vital capacity (FVC) over 2 years
      (percent predicted, measured according to American Thoracic Society standards), compared to
      conventional treatment alone in children with DMD.

      Secondary Objectives: To determine differences between children treated with LVR in addition
      to conventional treatment, compared to those treated with conventional treatment alone, in:
      (1) the number of courses of antibiotics, hospitalizations and intensive care admissions for
      respiratory exacerbations, (2) health-related quality of life, and (3) peak cough flow and
      other pulmonary function tests.

      Methods: We propose a 3-year multi-centre randomized controlled trial involving fifteen
      tertiary care pediatric hospitals across Canada. The study population consists of boys aged
      6-16 years with DMD and FVC ≥ 30% of predicted. A sample size of 110 participants will be
      enrolled. This has been informed by chart review and survey of participating centres to be
      feasible, and will be re-assessed with an ongoing internal pilot study. Intervention:
      Participants will be allocated with a minimization procedure to receive conventional
      treatment (non-invasive ventilation, nutritional supplementation, physiotherapy and/or
      antibiotics, as decided by the treating physician) or conventional treatment plus twice daily
      LVR exercises performed with an inexpensive, portable self-inflating resuscitation bag
      containing a one-way valve and a mouthpiece. Data Analysis: The primary outcome (change in
      percent predicted FVC over 2 years) will be compared between the two study groups using an
      analysis of co-variance (ANCOVA) that takes into account baseline FVC and minimization
      factors.

      Importance: Decline in pulmonary function among children with DMD negatively affects quality
      of life and predicts mortality. The relatively simple strategy of LVR has the potential to
      optimize pulmonary function and reduce respiratory exacerbations, thereby improving quality
      of life for individuals with DMD. This study is novel in that it is the first randomized
      controlled trial of LVR. A major strength is that the results will give support or refute
      recommendations regarding inclusion of LVR in the standard of care for individuals with DMD
      worldwide.
    

Intervention name(s): Lung Volume Recruitment (LVR); Conventional Treatment
Intervention type(s): Device; Other
Intervention description(s): LVR will be used twice per day; This may include: a. Physiotherapy, consisting of percussion, active cycle of breathing and/or postural drainage; b. Nutritional support, consisting of oral or tube-fed dietary supplements; c. Antibiotics (oral or intravenous), if there is evidence of respiratory infection; d. Non-invasive positive pressure ventilation, if there is evidence of nocturnal hypoventilation or sleep-disordered breathing; e. Systemic steroids
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Duchenne Muscular Dystrophy; Pulmonary complications; Lung volume recruitment,; Breath-stacking,; Cough efficacy,; Maximal insufflation capacity