The overall aim of this thesis was to identify outcome measures in Duchenne muscular dystrophy (DMD), specifically for non-ambulant patients, that are able to detect a clinically relevant... Show moreThe overall aim of this thesis was to identify outcome measures in Duchenne muscular dystrophy (DMD), specifically for non-ambulant patients, that are able to detect a clinically relevant difference in a relatively short period of time compatible with the duration of a clinical trial. The use of such outcome measures could lead to smaller sample sizes in such trials with a lower burden for patients. Show less
Hogrel, J.Y.; Decostre, V.; Ledoux, I.; Antonio, M. de; Niks, E.H.; Groot, I. de; ... ; Servais, L. 2020
Objective The main aim was to explore the changes in hand-grip strength in patients with Duchenne muscular dystrophy (DMD) aged 5-29 years. Secondary aims were to test the effect of mutation,... Show moreObjective The main aim was to explore the changes in hand-grip strength in patients with Duchenne muscular dystrophy (DMD) aged 5-29 years. Secondary aims were to test the effect of mutation, ambulatory status and glucocorticoid use on grip strength and its changes over time and to compute the number of subjects needed for a clinical trial to stabilize grip strength. Methods The analysis was performed on data collected during five international natural history studies on a cohort of DMD patients. Two hundred and two patients with genetically proven DMD were pooled from five different natural history studies. Excepting 13 patients with only one visit, the mean duration of follow-up was 2.2 +/- 1.6 years. A total of 977 measurement points were collected. Grip strength was measured on the dominant side with a high precision dynamometer. The analysis was performed using absolute values and normalized values expressed in percentage of predicted values for age. Results For absolute values, grip strength typically increased in ambulatory boys and decreased in non-ambulatory patients. However, when normalized, grip strength was already reduced at age 5 years and thereafter continued to fall away from normal values. The weaker the patients, the less strength they are prone to lose over again. Interpretation Grip strength constitutes a sensitive and continuous outcome measure that can be used across all stages of DMD. Its measurement is easy to standardized, can be used in ambulatory and non-ambulatory patients and does not present any floor or ceiling effect. It is thus attractive as an outcome measure in therapeutic trials. Show less
