Clinical Trial: Double Push Acoustic Radiation Force (DP ARF) Ultrasound for Monitoring Degeneration in Duchenne Muscular Dystrophy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Double Push Acoustic Radiation Force (DP ARF) Ultrasound for Monitoring Muscle Degeneration in Duchenne Muscular Dystrophy

Brief Summary: This is a pilot clinical trial to assess the ability of a new ultrasound-based imaging method, Double-Push Acoustic Radiation Force (DP ARF) ultrasound, to monitor the progression of Duchenne muscular dystrophy. The hypothesis being tested is that DP ARF ultrasound delineates changes in muscle composition and function in individual dystrophic muscles, from early through late stages of disease development, that correlate to time to loss of ambulation in patient volunteers.

Detailed Summary:

Double Push Acoustic Radiation Force (DP ARF) imaging will be performed in 3 cohorts of up to 10 boys with DMD and in age-matched boys with no known neuromuscular disorders.

The first DMD cohort will enroll at age 5-6, the second at age 7-8, and the third at age 9-10. The rectus femoris (RF), cranial sartorius (CS), gastrocnemius (GAST), and lateral deltoid (DT) muscles will be targeted for their known phenotypic variation in response to dystrophin deficiency. The RF undergoes early necrosis and fatty deposition, the CS is thought to be relatively spared, and the GAST seems to undergo true hypertrophy. The DT, which undergoes hypertrophy like the GAST, will also be examined to determine if the impact of dystrophin deficiency varies between upper and lower limbs. All boys will be imaged 3 times annually for 4 years. In addition to DP ARF imaging every 4 mos, the boys will undergo standard quantitative muscle testing (QMT) and timed function tests (TFT) of time to standing, 6-minute walk, and 30-feet walk. Age at loss of ambulation will also be recorded for each boy. Boys with DMD generally loose ambulation by age 10, so we expect that the 20 boys in the 7-11 and 9-13 aged cohorts will lose ambulation over the course of this study. The 10 boys in the 5-9 aged cohort will likely not lose ambulation during the study. Because the primary objective of this clinical investigation is to evaluate the potential of DP ARF imaging as a relevant surrogate for monitoring disease progression and response to therapies, the focus of the study will be on correlating DP ARF results to change in functional degeneration and time to loss of ambulation.

There are two experimental components to this study beyond what is standard practice for DMD patients: 1) DP ARF ultrasound imaging of the rectus femoris (RF), cranial sartorius (CS), gastrocnemi
Sponsor: University of North Carolina, Chapel Hill

Current Primary Outcome: Change in DP ARF marginal peak displacement [ Time Frame: once every 4 months for 4 years for 12 total measures ]

Marginal peak displacement (MPD) is a metric developed to qualitatively describe the degree of nonlinearity in the viscoelastic properties of tissue: MPD = (P2-D)/P1, where P1 and P2 are the first and second peak displacement achieved in tissue by the first and second ARF excitations, respectively, and d is the ARF-induced displacement remaining at the time of the second push.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Rate of change in DP ARF marginal peak displacement [ Time Frame: 4 months to 4 years ]
    rates of change in marginal peak displacement will be measured from time-point to time-point (every 4 months) and across multiple time points (spanning 8 months to 4 years).
  • Change in quantitative muscle testing score of maximum voluntary isometric contraction (MVIC) [ Time Frame: every 4 months for 4 years ]
    standard quantitative muscle testing of maximum voluntary isometric contraction (MVIC) in the rectus femoris, cranial sartorius, gastrocnemius, and lateral deltoid muscles of the right limbs.
  • Change in time to rise from supine position to standing [ Time Frame: every 4 months for 4 years ]
    standard time to standing timed function test
  • Change in distance walked in six minutes [ Time Frame: every 4 months for 4 years ]
    standard six-minute walk timed function test
  • Change in time to walk 30 feet [ Time Frame: every 4 months for 4 years ]
    standard 30-feet walk timed function test
  • Rate of change in maximum voluntary isometric contraction (MVIC) [ Time Frame: 4 months to 4 years ]
    rate of change in maximum voluntary isometric contraction (MVIC) will be assessed from time-point to time-point (4 month separation between measures) and across time-points (8 months to 4 years time separation between measures).
  • Rate of change in time to rise from supine to standing position [ Time Frame: 4 months to 4 years ]
    rate of change in time to standing timed function test score will be assessed from time-point to time-point (4 month separation between measures) and across time-points (8 months to 4 years time separation between measures).
  • Rate of change in distance walked in six minutes [ Time Frame: 4 months to 4 years ]
    rate of change in six-minute walk timed function test score will be assessed from time-point to time-point (4 month separation between measures) and across time-points (8 months to 4 years time separation between measures).
  • Rate of change in time to walk 30 feet [ Time Frame: 4 months to 4 years ]
    rate of change in 30-feet walk timed function test score will be assessed from time-point to time-point (4 month separation between measures) and across time-points (8 months to 4 years time separation between measures).
  • Age at loss of ambulation [ Time Frame: 4 years ]
    Loss of ambulation will be diagnosed by the patient volunteer's physician. The patient volunteer's age at the time loss of ambulation is first diagnosed will be recorded.
  • Change in percent degenerative muscle composition [ Time Frame: every 4 months for 4 years ]
    Muscle boundaries will be hand-delineated using matched B-Mode image guidance in DP ARF marginal peak displacement parametric images. Within each 2D muscle image, percent degenerative area (Ad) will be calculated as T/N, where N is the total muscle area (number of pixels x area/pixel) and T is the muscle area in which marginal peak displacement values are within thresholds for necrosis, fat or fibrous tissue identification.
  • Change in percent necrotic tissue area [ Time Frame: every 4 months for 4 years ]
    Muscle boundaries will be hand-delineated using matched B-Mode image guidance in DP ARF marginal peak displacement parametric images. Within each 2D muscle image, percent necrotic area (An) will be calculated as n/N, where N is the total muscle area (number of pixels x area/pixel) and n is the muscle area in which marginal peak displacement values are within thresholds for necrosis.
  • Change in percent fat tissue area [ Time Frame: every 4 months for 4 years ]
    Muscle boundaries will be hand-delineated using matched B-Mode image guidance in DP ARF marginal peak displacement parametric images. Within each 2D muscle image, percent fatty deposition area (Af) will be calculated as f/N, where N is the total muscle area (number of pixels x area/pixel) and f is the muscle area in which marginal peak displacement values are within thresholds for fat tissue identification.
  • Change in percent fibrotic tissue area [ Time Frame: every 4 months for 4 years ]
    Muscle boundaries will be hand-delineated using matched B-Mode image guidance in DP ARF marginal peak displacement parametric images. Within each 2D muscle image, percent degenerative area (Ac) will be calculated as c/N, where N is the total muscle area (number of pixels x area/pixel) and c is the muscle area in which marginal peak displacement values are within thresholds for fibrous tissue identification.


Original Secondary Outcome: Same as current

Information By: University of North Carolina, Chapel Hill

Dates:
Date Received: December 22, 2011
Date Started: January 2012
Date Completion: September 2018
Last Updated: January 12, 2017
Last Verified: January 2017