T.P.7: Prediction equation to estimate 6-Minute-Walk-Distance from motor function tests in patients with Duchenne Muscular Dystrophy

Abstract

6-Minute Walk Distance (6MWD) has been used as the primary outcome measure for clinical trials in ambulatory patients with Duchenne Muscular Dystrophy (DMD). Unlike the Gower's Maneuver (G), 10-m walk/run (W/R) and North Star Ambulatory Assessment (NSAA) tests, the 6-min Walk Test (6MWT) is not routinely performed in clinic. Prediction of 6MWD with clinical motor function tests would facilitate in-clinic pre-screening of DMD patients for clinical trials, reduce screening failure rates and costs for clinical trials. To predict 6MWD from G, W/R and NSAA data Retrospective review of motor screening data (6WMD, G, W/R and NSAA) for the IGF1, EIM, ataluren, drisapersen and DMD natural history studies at our center. Velocity (<i>V</i>) was calculated from the <i>W</i>/<i>R</i> test. Linear regression was use to fit the 6MWD vs the other variables separately. SAS version 9.3 was used for statistical analyses. Study population: <i>N</i>=107; mean age of subjects is 9.28±2.96years; all subjects are on corticosteroid treatment (CS); mean age of starting CS is 5.55±1.69years; mean duration of CS is 3.78 ±2.68years; mean 6MWD for this cohort is 399.4±78.2. There are significant correlations between the clinical motor function test results and 6MWD. The correlation coefficients are −0.54, −0.77, 0.76 and 0.75 for <i>G</i>, <i>W</i>/<i>R</i>, <i>V</i> and NSAA vs 6MWD respectively (all <i>p</i>< 0,0001). <i>W</i>/<i>R</i>, <i>V</i> and NSAA could be used independently to predict 6MWD: 6MWD=575–34∗<i>W</i>/<i>R</i> (R2=0.60); 6MWD=172 +107*V (R2=0.57) and 6MWD=208 +8*NSAA (R2=0.56). Using NSAA and either <i>W</i>/<i>R</i> (R2=0.62) or <i>V</i> (R2=0.61) in a two-variable regression improves the regression fit slightly. Overall, <i>G</i>, <i>V</i> and NSAA are highly correlated with 6MWD; with greater correlations with <i>W</i>/<i>R</i>, <i>V</i> and NSAA. The NSAA and 10m walk/run test may be useful tools in clinics to predict 6MWD, thereby enabling time and cost efficient pre-screening of clinic patients for ambulatory DMD trials.