Clinical Trials Logo

Clinical Trial Summary

Background:

- Duchenne muscular dystrophy (DMD) is a disease in which the muscles are unable to make the protein dystrophin. Without this protein, the muscles become gradually weaker. A new medicine called GSK2402968 is being tested to see if it can help prevent or slow down this loss of muscle strength. In this study, boys with DMD and healthy volunteers will have different types of imaging studies to see which ones provide the best images of the muscles. This information will help researchers use these imaging techniques to test the safety and effectiveness of GSK2402968 and other agents.

Objectives:

- To test magnetic resonance imaging and ultrasound techniques that can detect changes in muscles of boys with DMD.

Eligibility:

- Boys who have DMD and are in the GSK2402968 drug test study.

- Healthy boys of the same age as the above study participants.

Design:

- Participants will be screened with a medical history and physical exam.

- Healthy volunteers will have one 2-hour visit with three tests. Magnetic resonance imaging (MRI) scans of the skeletal muscles and heart and diaphragm muscles will be carried out. Muscle ultrasound imaging of leg and arm muscles will also be done. Participants should not perform heavy physical activity like school sports or long walks during the week before the visit.

- Participants in the GSK2402968 study will have the same series of tests as the healthy volunteers. The tests will be given during the study screening phase. They will be repeated after 3 months and 6 months of receiving the study agent (GSK2402968 or placebo) and at 6 months after stopping the GSK study.


Clinical Trial Description

Objective:

Duchenne muscular dystrophy (DMD) is the most frequent inherited fatal childhood disease. Antisense oligonucleotide (AON)-induced exon skipping is a promising therapeutic strategy for DMD that is currently being explored in clinical trials. Magnetic resonance imaging (MRI) and ultrasound imaging methods are sensitive to key processes in dystrophic muscle such as edema and fat infiltration and therefore could serve as a biomarker of disease progression and therapeutic response. Our objective is to explore the potential of these imaging biomarkers for GSK2402968 (AON) effects in ambulatory boys with DMD. The primary objective is to assess longitudinal changes in skeletal muscle structural MRI measures reflecting fat and edema in the lower extremities in ambulatory boys with DMD receiving GSK2402968 or placebo

Study Population:

We aim to enroll up to 65 ambulatory boys with DMD. Healthy volunteer/control boys (up to 25) matched for the age-range will be recruited to obtain pilot data for imaging studies.

Design:

This prospective study of skeletal muscle, cardiac, and diaphragm imaging at the NIH will be offered to all subjects participating in a phase 2, double blind, exploratory parallel-group, placebo-controlled clinical study in ambulatory subjects with DMD resulting from a mutation that can be corrected by exon 51 skipping induced by GSK2402968 (parent study; DMD114876). Subjects will travel with a family member to the NIH for MRI and ultrasound assessments during the screening phase of the parent study or up to 3 weeks after randomization and additionally at the following time points in the parent study: at 12 weeks ( 3 weeks), and 24 weeks ( 3 weeks) during the blinded treatment period; and finally, after completion of 24 week post-treatment phase (at 48 weeks 4 weeks). If not randomized, the subjects will have a one-time evaluation during the screening phase of the parent study. Pilot data also will be obtained from healthy boys (matched for the age-range) for comparisons to allow exploration of MRI and ultrasound measures specific to pathology in the ambulatory boys with DMD. Subjects will not be treated with GSK2402968 or any other experimental drug at the NIH. There are no follow-up or termination procedures for this study.

Outcome Measures:

Primary Outcome Measure: MRI changes in skeletal muscle percent fat in the lower extremities using T1w GRE Dixon method at 24 weeks from baseline in the parent study in ambulatory boys with DMD receiving GSK2402968 or placebo. Secondary outcome measures: Differences in the following outcome measures between healthy boys and ambulatory boys with DMD at baseline; and changes in these measures over time in the parent study at 12 weeks, 24 weeks, and 48 weeks from baseline in ambulatory boys with DMD receiving GSK2402968 or placebo: 1. Skeletal muscle MRI: relative muscle fat/water quantified by T1w GRE Dixon imaging method in skeletal muscles; Muscle edema assessed by T2 imaging; Muscle fat/water content and edema additionally quantified by IDEAL-CPMG method; and 2. Cardiac MRI: Cardiac function (ejection fraction/ LV function) assessed by SSFP Cine MRI and manual planimetry of LV volumes and mass at end systole and end diastole; Myocardial fat content assessed by Multiecho Dixon Fat /Water Separation method; Myocardial edema assessed by T2 quantification; Myocardial T1 assessed by MOLLI (modified Look-Locker Inversion recovery).

Exploratory Outcome Measures: MRI changes in muscle architecture and water diffusivity will be assessed by Diffusion EPI MRI. If well tolerated, then we will use a portable device (Ankle IntelliStretch device, RehabTek) to study the effects of exercise on selected MRI measures in leg muscles. Muscle ultrasound will be used to monitor changes in skeletal muscle volume, echogenicity and stiffness. Dynamic breathing MRI will be performed to measure diaphragm motion during free breathing and voluntary maximal inspiration and exhalation. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01451281
Study type Observational
Source National Institutes of Health Clinical Center (CC)
Contact
Status Completed
Phase
Start date September 15, 2011
Completion date May 20, 2019

See also
  Status Clinical Trial Phase
Recruiting NCT01834066 - Study Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Muscular Dystrophy. Phase 1/Phase 2
Recruiting NCT01834040 - Study Safety and Efficacy of BMMNC for the Patient With Duchenne Muscular Dystrophy Phase 1/Phase 2
Recruiting NCT00082108 - Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
Recruiting NCT00138931 - Genetics of Cardiovascular and Neuromuscular Disease
Completed NCT00622453 - Arrhythmias in Myotonic Muscular Dystrophy N/A
Active, not recruiting NCT04038138 - Clinical Trial Readiness Network FSHD France: Prospective 24 Months MRI Study N/A
Not yet recruiting NCT05470478 - iBCI Optimization for Veterans With Paralysis N/A
Completed NCT04154098 - Evaluation of a Textile Scapula Orthosis N/A
Terminated NCT02653833 - The Study of Skeletal Muscle Blood Flow in Becker Muscular Dystrophy Early Phase 1
Not yet recruiting NCT06363526 - Effectiveness of 5-week Digital Respiratory Practice in a Group of Children With Duchenne Muscular Dystrophy and Becker Muscular Dystrophy. N/A
Completed NCT01990976 - Study of Morphology and Functional Magnetic Resonance Imaging (MRI) Muscle Patients With Muscular Dystrophy Type FSHD Benefiting a Physical Training Introduced. N/A
Completed NCT01393444 - ECoG Direct Brain Interface for Individuals With Upper Limb Paralysis N/A
Recruiting NCT00912041 - BrainGate2: Feasibility Study of an Intracortical Neural Interface System for Persons With Tetraplegia N/A
Completed NCT00866112 - A Randomized Exercise Trial for Wheelchair Users N/A
Completed NCT01882400 - Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy Phase 4
Recruiting NCT05726591 - Evaluating Long-term Use of a Pediatric Robotic Exoskeleton (P.REX/Agilik) to Improve Gait in Children With Movement Disorders N/A
Completed NCT02815878 - Enhance Wellness for Individuals With Long-Term Physical Disabilities N/A
Completed NCT04035967 - Investigation of Parents' Anxiety Level and Health Related Quality of Life in Different Types of Physical Disabilities
Not yet recruiting NCT06290713 - Vasodilator and Exercise Study for DMD (VASO-REx) Phase 2
Recruiting NCT05230459 - A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1) Phase 1/Phase 2