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

Harneet Arora, Rebecca J Willcocks, Donovan J Lott, Ann T Harrington, Claudia R Senesac, Kirsten L Zilke, Michael J Daniels, Dandan Xu, Gihan I Tennekoon, Erika L Finanger, Barry S Russman, Richard S Finkel, William T Triplett, Barry J Byrne, Glenn A Walter, H Lee Sweeney, Krista Vandenborne, Harneet Arora, Rebecca J Willcocks, Donovan J Lott, Ann T Harrington, Claudia R Senesac, Kirsten L Zilke, Michael J Daniels, Dandan Xu, Gihan I Tennekoon, Erika L Finanger, Barry S Russman, Richard S Finkel, William T Triplett, Barry J Byrne, Glenn A Walter, H Lee Sweeney, Krista Vandenborne

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.

Conflict of interest statement

Conflict of interest: None of the authors has any conflict of interest to disclose.

Figures

Figure 1. Decline in 6 minute walk… — **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

**Figure 2. Change over 1 year for…**

**Figure 2. Change over 1 year for all functional tests for all age groups in…**

**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…**

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

**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…**

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

As the study…

**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…**

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

**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.

See this image and copyright information in PMC

Figure 2. Change over 1 year for… — **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… — **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… — **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… — **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.

Source: PubMed

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

Abstract

Conflict of interest statement

Figures

スポンサーと協力者

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