A Study to Test Lung Stretch Therapy (Hyperinsufflation) in Children With Collagen VI Muscular Dystrophy

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.