Longitudinal timed function tests in Duchenne muscular dystrophy: ImagingDMD cohort natural history

Abstract

Introduction: Tests of ambulatory function are common clinical trial endpoints in Duchenne muscular dystrophy (DMD). Using these tests, the ImagingDMD study has generated a large data set that can describe the contemporary natural history of DMD in 5-12.9-year-olds.

Methods: Ninety-two corticosteroid-treated boys with DMD and 45 controls participated in this longitudinal study. Participants performed the 6-minute walk test (6MWT) and timed function tests (TFT: 10-m walk/run, climbing 4 stairs, supine to stand).

Results: Boys with DMD had impaired functional performance even at 5-6.9 years old. Boys older than 7 had significant declines in function over 1 year for 10-m walk/run and 6MWT. Eighty percent of participants could perform all functional tests at 9 years old. TFTs appear to be slightly more responsive and predictive of disease progression than the 6MWT in 7-12.9 year olds.

Discussion: This study provides insight into the contemporary natural history of key functional endpoints in DMD. Muscle Nerve 58: 631-638, 2018.

Keywords: 6-minute walk test; Duchenne muscular dystrophy; ambulatory function; functional endpoints; loss of ambulation; outcome measures.

Figure 1. Decline in 6 minute walk test performance over 1 year across ages

A significant decline in 6 minute walk test over 1 year was found for boys >7 years of age for both (a) 6 minute walk test and (b) percentage predicted 6 minute walk test, p <0.05.

Figure 2. Change over 1 year for all functional tests for all age groups in boys with DMD. BL= Baseline

Overall there was a shift to slower times/shorter distance in boys aged >7 years, but not in younger boys. Data represent 19 boys aged 5 – 6.9, 23 boys aged 7 – 8.9, 22 boys aged 9 – 10.9, and 16 boys aged 11 – 12.9. Missing data or invalid data did not exceed 10% for any test in any age group.

Figure 3. Clinically important change in functional tests over 1 year by baseline 6 minute walk distance

Subjects with lower baseline 6 minute walk test distances were more likely to experience declines in functional performance or loss of functional ability over 1 year on timed function tests but not the 6 minute walk test itself.

Figure 4. Heterogeneity in 6 minute walk test performance over 48 months

As the study progressed, an increasing number of boys lost ambulation. However, some boys were able to maintain performance over up to 4 years, notably all those with baseline 6MWD ≥451m.

Figure 5. Number of subjects who are still able to perform each functional test by age

At 9 years old, more than 80 % of boys could still perform all functional tests. At 12 years of age, more than 80% subjects could perform functional tests except the supine to stand, which only about 40% could perform. By 14 years old, about half of the boys were unable to perform any of the functional tests.