A Study to Test Lung Stretch Therapy (Hyperinsufflation) in Children With Collagen VI Muscular Dystrophy
Condition: Congenital Muscular Dystrophy
MeSH terms: Muscular Dystrophies
Study type: Interventional

Summary: 
      This research study includes children ages 5 to 20 years old with Collagen Type 6 Congenital
      Muscular Dystrophy or Laminin α2-related muscular dystrophy (LAMA2-MD). The goal of this
      study is to measure the effect of breathing exercise to stretch the chest in slowing the loss
      of breathing function. The breathing stretches are done with a machine called Cough Assist®.

      The study is being done at Cincinnati Children's Hospital Medical Center and Children's
      Hospital of Philadelphia. The study involves traveling to one of these 2 centers for 4 visits
      over 13 months. The study also includes 3 sets of phone visits called Daily Phone Diaries.

      Participants will be "randomized" into one of 2 study groups in a 1:1 ratio. The treatment
      group will use the Cough Assist® machine twice a day for 15 minutes. The control group will
      continue with their current daily care. The Cough Assist® is a machine that blows air into
      the lungs (insufflation) and helps pull air out of the lungs. The investigators will be
      blowing enough air into the lungs to cause a stretch to the chest. This is called
      hyperinsufflation.

      Study visits will last about 5 to 6 hours and will include medical and quality of life
      questionnaires and pulmonary function tests to determine lung function and the individualized
      settings to be prescribed for the Cough Assist®.
    

Detailed description: 
      Congenital muscular dystrophy (CMD) secondary to collagen VI deficiency and Laminin
      α2-related muscular dystrophy (LAMA2-MD) are distinct genetic neuromuscular disorders
      presenting from birth. Respiratory failure is the principal cause of morbidity and mortality
      from the disease. As CMD has no existing treatment, the majority of affected children develop
      respiratory failure and require non-invasive ventilation between the first and second decades
      of life. There is evidence that in muscular dystrophy the progressive decrease in lung volume
      is disproportionally greater than anticipated for the degree of respiratory muscle weakness.
      Chest wall stiffness and decreased lung elasticity which collectively diminish compliance of
      the respiratory system are believed to be important contributors to the disproportionate
      decrease in lung volume. The investigators' research aims at testing the hypothesis that in
      subjects with CMD Collagen VI and LAMA2-MD, daily passive stretch of the chest wall through
      lung hyperinsufflation therapy could slow down the annual rate of decline in lung volume,
      delay the onset of respiratory failure and improve quality of life.

      This is a randomized, controlled, interventional study. The intervention consists of an
      individualized hyperinsufflation titration protocol. The duration of the active protocol will
      last 12 months. Because CMD presents a limited subject pool, this study is a partnership with
      Cincinnati Children's Hospital of Cincinnati (CCHMC) and Children's Hospital of Philadelphia
      (CHOP) with approximately half of the studies being done at each site. Potential subjects
      will be identified through Cure CMD international registry and disease specific websites to
      meet the needed number of subjects.

      At Visit 1, subjects will have their baseline assessments, QOL (quality of Life)
      questionnaires, and pressure titration and hyperinsufflation protocol to determine Peak
      Insufflation Pressure (PIP). Subjects will be given their randomization assignment into
      either the Treatment or Control arm. Both groups will have pressure titration and
      hyperinsufflation protocols for Peak Insufflation Pressure (PIP) at each study visit.

      For the Treatment Group, participants at Visit 1 will leave with prescription settings on the
      Cough Assist® device and they will begin the 12 month interventional period with 15 minute,
      twice daily hyperinsufflation treatments. Between visits, the Treatment group will mail back
      the information card (SD card) from the Cough Assist to measure adherence. All visits will be
      identical for both treatment and control group and will include all the activities from Visit
      1 except for randomization.

      There will be 3 scheduled phone visits for the Daily Phone Diary (DPD) encounters. The DPD is
      a phone-based diary that tracks patients and / or caregivers through their activities over
      the past 24 hours using a cued recall procedure. A set of two DPDs (one weekday and one
      weekend day) is conducted by phone at each of the 3 assessment points.

      The investigators anticipate a significant number of subjects will live greater than 100
      miles from the research centers. Travel arrangements will be made by family and paid for by
      the study through additional funding provided by Cure CMD.
    

Intervention name(s): Hyperinsufflation therapy
Intervention type(s): Other
Intervention description(s): 15 minutes twice a day of hyperinsufflation with Cough Assist® device
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Congenital Muscular Dystrophy; Collagen VI Deficiency; Hyperinsufflation; Cough Assist; LAMA2- Muscular Dystrophy