Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
|Muscular Dystrophies Duchenne Muscular Dystrophy Becker Muscular Dystrophy Limb-Girdle Muscular Dystrophy||Other: Retrograde high pressure transvenous perfusion with normal saline||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Safety and Feasibility of Transvenous Limb Perfusion With Normal Saline in Human Muscular Dystrophy|
- Muscle, Nerve, or Vascular Damage [ Time Frame: Measured within 2 weeks after limb perfusion procedure ]
Number of Participants with all of the following three:
- Unchanged Doppler ultrasound to assess venous and arterial damage pre-and post perfusion based on report
- Without clinically significant changes in electrodiagnostic testing using standard neurographic techniques pre-and post perfusion:>1 mSec change in baseline distal motor latency; <75% baseline compound muscle action potential amplitude, <75% baseline conduction velocity, sensory nerve action potential
- Without clinically significant changes in Quantitative muscle testing (QMT) strength assessments pre-and post perfusion:< 85% baseline
|Study Start Date:||March 2009|
|Study Completion Date:||February 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Participants will undergo retrograde high pressure transvenous limb perfusion with normal saline.
Other: Retrograde high pressure transvenous perfusion with normal saline
Dose escalation of saline volume, infusion rate, and tourniquet pressure, as determined in a stepwise manner and by careful monitoring
There are many types of muscular dystrophies, all of which are progressive, degenerative genetic disorders. One type is Becker's muscular dystrophy, which involves slowly worsening muscle weakness of the legs and pelvis and which can lead to cardiomyopathy, deformities, respiratory failure, and permanent disability. Limb-girdle muscular dystrophy, another type, is also characterized by progressive muscle weakness, first affecting the muscles around the shoulder girdle and hips and possibly affecting other muscles as the disorder progresses. Complications of limb-girdle muscular dystrophy can include abnormal heart rhythms, joint contractures, difficulties with activities of daily living, significant loss of mobility, and permanent disability. There is no cure for muscular dystrophies. Current treatments, such as steroids, mobility aids, physical therapy, and respiratory care, can decrease some of the complications, but there is a clear need for a curative therapy.
The genetic basis of muscular dystrophies is well understood, which makes gene therapy a potential treatment option in the future. A key step in developing gene therapy involves first ensuring safe delivery of genetic material into a single limb of a patient before using active treatment in the patient's entire body. High-pressure, high-volume transvenous limb perfusion, in which fluid is forced under high pressure into arm and leg muscles through the veins, has shown the greatest potential as a delivery method. The purpose of this study is to determine the safety and feasibility of this method with normal saline in people who have Becker's muscular dystrophy or limb-girdle muscular dystrophy.
Participation in this study will last up to 4 weeks. At an initial baseline visit, participants will undergo water emersion measurements of their arm and leg, nerve testing, and muscle strength testing. About 1 to 2 weeks later, participants will enter the pediatric intensive care unit for up to 36 hours. During the inpatient stay, participants will undergo the high-pressure, high-volume transvenous limb perfusion procedure with normal saline in one of their arms or legs. Throughout the hospital stay, breathing, heart rate, and blood pressure will be monitored. Medication will be available to control any discomfort or pain experienced by participants. Each subsequent participant will receive more fluid pumped at a higher pressure and with a tighter tourniquet than the previous participant, as long as no problems or adverse effects are detected. Some of the participants will undergo an MRI immediately after the perfusion procedure. About 1 to 2 weeks after the inpatient stay, participants will attend a follow-up visit that will include repeat nerve and muscle strength testing, a blood draw, photos of limbs, and an ultrasound of the leg blood vessels if the participant's leg was used during the perfusion procedure.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00873782
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||William J. Powers, MD||University of North Carolina|