Reliable surrogate outcome measures in multicenter clinical trials of Duchenne muscular dystrophy.

We studied the reliability of a series of endpoints in an evaluation of subjects with Duchenne muscular dystrophy (DMD). The endpoints included quantitative muscle tests (QMTs), timed function tests, forced vital capacity (FVC), and manual muscle tests (MMT). Thirty-one ambulatory subjects with DMD (mean age 8.9 years; range 5-16 years) were evaluated at eight sites by 15 newly trained evaluators as a test of interrater reliability of outcome measures. Both total QMT score [intraclass correlation coefficient (ICC) 0.96] and individual QMT assessments (ICC 0.85-0.96) were highly reliable. Forced vital capacity and all timed function tests were also highly reliable (ICC 0.97-0.99). MMT was the least reliable assessment method (ICC 0.61). These data suggest that primary surrogate outcome measures in large multicenter clinical trials in DMD should use QMT, FVC, or time function tests to obtain maximum power and greatest sensitivity.

CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy.

We tested the efficacy and safety of glutamine (0.6 gm/kg/day) and creatine (5 gm/day) in 50 ambulant boys with Duchenne muscular dystrophy in a 6-month, double-blind, placebo-controlled clinical trial. Drug efficacy was tested by measuring muscle strength manually (34 muscle groups) and quantitatively (10 muscle groups). Timed functional tests, functional parameters, and pulmonary function tests were secondary outcome measures. Although there was no statistically significant effect of either therapy based on manual and quantitative measurements of muscle strength, a disease-modifying effect of creatine in older Duchenne muscular dystrophy and creatine and glutamine in younger Duchenne muscular dystrophy cannot be excluded. Creatine and glutamine were well tolerated.