Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
Condition: Muscular Dystrophies; Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Dystrophies, Limb-Girdle
Intervention: Retrograde high pressure transvenous perfusion with normal saline
Intervention description: Dose escalation of saline volume, infusion rate, and tourniquet pressure, as determined in a stepwise manner and by careful monitoring
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Limb Perfusion; Gene Therapy

Summary:

      Muscular dystrophies are inherited disorders in which the skeletal and heart muscles become
      progressively weaker, sometimes leading to permanent disability. Current treatments aim to
      control symptoms as much as possible, but there is no cure. Gene therapy, in which defective
      genes causing the disorder are corrected, is a potential treatment option and is in the
      process of being developed for muscular dystrophies. This study will determine the safety and
      feasibility of a particular delivery method for gene therapy that could be used in the future
      to treat people with muscular dystrophies. Only normal saline, and no active treatment, will
      be used in this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Duchenne or Becker muscular dystrophy, as defined by progressive weakness
             with onset before the age of 21, X-linked inheritance, and reduced dystrophin (less
             than 3%) on muscle biopsy OR mutation in the dystrophin gene

          -  Diagnosis of limb girdle muscular dystrophy, as defined by progressive weakness with
             onset before the age of 21, normal dystrophin on muscle biopsy OR proven mutation
             associated with one of the types of limb girdle dystrophy

          -  Older than 21 years of age and preferably younger 30 years of age

          -  Able to stand, independently or with assistance

          -  Able to communicate with pertinent staff

          -  Able to understand and willingly comply with the requirements of the study

        Exclusion Criteria:

          -  Confirmed diagnosis of any other muscle disease

          -  Previous compartment syndrome requiring surgical decompression

          -  Previous venous or arterial thrombosis other than superficial venous thrombosis
             associated with intravenous catheter

          -  Coagulopathy, including known diagnosis of bleeding diathesis, history of excessive
             bleeding on multiple occasions, or taking anticoagulant or platelet inhibitory
             medications

          -  Systemic arterial or venous disease (e.g., Raynaud's, aortic coarctation or aneurysm)

          -  Previous injury to selected limb with residual effect other than superficial scarring

          -  Previous vascular surgery to selected limb

          -  Previous compressive neuropathy (e.g., carpal tunnel syndrome in arm, peroneal palsy
             in leg)

          -  Complex regional pain syndrome or other neurological cause of limb pain

          -  Previous clinical diagnosis of congestive heart failure

          -  Previous echocardiography showing ejection fraction less than 40% or ventricular
             dilation

          -  Previous chest x-ray showing enlarged cardiac silhouette or pulmonary edema

          -  History of rhabdomyolysis with worsening renal function

          -  Creatinine greater than 1.7 mg/dL

          -  Resting hypoxemia with SaO2 less than 90% on room air

          -  Other significant heart, lung, or kidney disease that would compromise the body's
             capacity to handle a fluid load

          -  Previous forced vital capacity less than 75% of age and height adjusted norm, in the
             absence of acute reversible pulmonary disease

          -  Sickle cell disease (sickle cell anemia [SS] or sickle hemoglobin C disease [SC])

          -  Pregnant

          -  Non-English speaker