Clinical trial readiness study of distal myopathy and dysphagia in nephropathic cystinosis

Abstract

Background: Nephropathic cystinosis is a lysosomal storage disorder with late-onset systemic complications, such as myopathy and dysphagia. Currently employed outcome measures lack sensitivity and responsiveness for dysphagia and myopathy, a limitation to clinical trial readiness. Methods: We evaluated 20 patients with nephropathic cystinosis in two visits over the course of a year to identify outcomes sensitive to detect changes over time. Patients also underwent an expiratory muscle strength training program to assess any effects on aspiration and dysphagia. Results: There were significant differences in the Timed Up and Go Test (TUG) and Timed 25-Foot Walk (25-FW) between baseline and 1-y follow-up (P < .05). Maximum expiratory pressure (MEP) and peak cough flow (PCF) significantly improved following respiratory training (P < .05). Conclusions: Improved respiratory outcomes may enhance patients ability to expel aspirated material from the airway, stave off pulmonary sequelae associated with chronic aspiration, and yield an overall improvement in physical health and wellbeing.

Longitudinal dysphagia assessment in adult patients with nephropathic cystinosis using the Modified Barium Swallow Impairment Profile

“…There were many patients who reported dysphagia where the PAS was not sensitive enough to capture abnormalities 18–24 . In our initial survey, 12/20 (60%) patients reported some degree of difficulty swallowing; however, PAS captured dysfunction in only 3/20 patients (15%) 14,15 …”

“…As part of a prospective clinical trial readiness study, 14,15 we conducted video fluoroscopic swallowing studies (VFSS) at baseline and 1 y follow‐up. VFSS were analyzed using the Penetration Aspiration Scale (PAS) 16 .…”

“…12 Dysphagia may impair quality of life and lead to other complications including aspiration pneumonia. 13 As part of a prospective clinical trial readiness study, 14,15 we conducted video fluoroscopic swallowing studies (VFSS) at baseline and 1 y follow-up. VFSS were analyzed using the Penetration Aspiration Scale (PAS).…”

“…[18][19][20][21][22][23][24] In our initial survey, 12/20 (60%) patients reported some degree of difficulty swallowing; however, PAS captured dysfunction in only 3/20 patients (15%). 14,15 More modern techniques such as the Modified Barium Swallow Impairment Profile (MBSImP) have been applied to different neurological disorders such as myositis and have captured more subtle changes, thereby helping understand the pattern of muscle involvement implicated in dysphagia. 17 MBSImP assesses 17 specific physiologic components of swallow function, allowing the clinician to examine where disordered function correlates with patient experience.…”

Cystinosis myopathy: Searching for optimal clinical outcome measures

“…In this issue of Muscle & Nerve , Sadjadi et al reported the results of their prospective study on clinical trial readiness of distal myopathy and dysphagia in nephropathic cystinosis 8 . In visit 1, the authors evaluated 20 nephropathic cystinosis patients (7 male and 13 female, age range 20‐64 years) 9 .…”