Clinical trial readiness study of myopathy, dyspnea and dysphagia in patients with nephropathic cystinosis

Nephropathic cystinosis is a lysosomal storage disorder manifesting in early renal failure and anemia often requiring hemodialysis and kidney transplant. Prolonged patient survival following renal transplantation has revealed late-onset systemic complications, including the development of myopathy and dysphagia. Currently employed outcome measures lack sensitivity and responsiveness for evaluation of dysphagia in patients with nephropathic cystinosis. 

We evaluated 20 patients with nephropathic cystinosis (median age 28.5) in two visits (visit1, visit2) over the course of one year to identify outcomes sensitive to detect changes over time. Following the observational phase of the study, patients underwent a 5-week exercise regimen using an EMST-150 respiratory trainer to identify any effect on aspiration and dysphagia (visit3).

There were no significant changes in M.D.Anderson Dysphagia Inventory and Eating-Assessment-Tool, grip dynamomyometry over the course of the observational phase of the study or following exercise regimen. There were significant differences between Timed-Up&Go (visit1, mean 7.0, 95%CI [6.3;7.8]; visit2, mean 7.9, 95%CI [7.0;8.8]) and 25-Foot-Walk (visit1, mean 4.9, 95%CI [4.5;5.4]; visit2, mean 5.7, 95%CI [5.2;6.3]). Maximum Expiratory Pressure (visit2, mean 63.4, 95%CI [45.4;81.4]; visit3, mean 80.9, 95%CI [60.4; 101.5]) and Peak Cough Flow (visit2, mean 233.2, 95%CI [184.9;281.5]; visit3, mean 258.0, 95%CI [207.5;310.5]) significantly improved following respiratory training. Videofluoroscopic evaluation at visit 3 was notable for improvement in three patients with baseline high Penetration-Aspiration-Scale scores.

Patients with more severe dysphagia showed modest improvements in the dysphagia score following the exercise regimen, suggesting possible benefit in more severely affected patients and pointing to the value of stratification in future trials. Improved respiratory measures may enhance the ability to expel aspirated material from the airway, prevent pulmonary sequelae associated with chronic aspiration, and yield an overall improvement in physical health and well being.