Lessons for future clinical trials in adults with Becker muscular dystrophy: Disease progression detected by muscle magnetic resonance imaging, clinical and patient-reported outcome measures

Eur J Neurol. 2024 Jul;31(7):e16282. doi: 10.1111/ene.16282. Epub 2024 Mar 20.

Abstract

Background and purpose: Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials.

Methods: Muscle magnetic resonance imaging, patient-reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed-function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow-up.

Results: Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32-item Motor Function Measurement (MFM-32) scale (-1.3%, p = 0.017), North Star Ambulatory Assessment (-1.3 points, p = 0.010) and patient-reported activity limitations scale (-0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6-min walk distance (-28.7 m, p = 0.042), 10-m walking test (-0.1 m/s, p = 0.032), time to climb four stairs test (-0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (-4.6 N m, p = 0.014) and hamstrings (-5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM-32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15).

Discussion: It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow-up. Finally, significant changes are reported in a wide range of clinical and patient-reported outcome measures, of which the MFM-32 appeared to be the most sensitive to change in adults with BMD.

Keywords: BMD; Dixon; magnetic resonance imaging; quantitative MRI; trial readiness.

MeSH terms

  • Adult
  • Clinical Trials as Topic
  • Disease Progression*
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Muscle Strength / physiology
  • Muscle, Skeletal* / diagnostic imaging
  • Muscle, Skeletal* / physiopathology
  • Muscular Dystrophy, Duchenne* / diagnostic imaging
  • Muscular Dystrophy, Duchenne* / physiopathology
  • Patient Reported Outcome Measures*
  • Young Adult