Muscular DystrophiesPhase 1NCT00873782
Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
A Phase 1 study testing Retrograde high pressure transvenous perfusion with normal saline in people with Muscular Dystrophies and Duchenne Muscular Dystrophy, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Muscular Dystrophies, Duchenne Muscular Dystrophy, Becker Muscular Dystrophy
- What is being tested?
- Retrograde high pressure transvenous perfusion with normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Feb 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: Safety and Feasibility of Transvenous Limb Perfusion With Normal Saline in Human Muscular Dystrophy
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.
Read the detailed description
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.
- Conditions
- Muscular Dystrophies, Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Limb-Girdle Muscular Dystrophy
- Being tested
- Retrograde high pressure transvenous perfusion with normal saline
- Keywords
- Limb Perfusion, Gene Therapy
- Medical subject headings
- Muscular Dystrophies, Muscular Dystrophy, Duchenne, Muscular Dystrophies, Limb-Girdle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retrograde high pressure transvenous perfusion with normal salineOther
Dose escalation of saline volume, infusion rate, and tourniquet pressure, as determined in a stepwise manner and by careful monitoring
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will undergo retrograde high pressure transvenous limb perfusion with normal saline. Receives: Other: Retrograde high pressure transvenous perfusion with normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle, Nerve, or Vascular Damage
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
Measured: Measured within 2 weeks after limb perfusion procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2009 (estimated)
- Study startMar 2009
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Muscular DystrophiesStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), University of North Carolina
- Responsible party
- Principal investigator, William Powers, University of North Carolina, Chapel Hill
- Investigators
- William J. Powers, MD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00873782
- Sponsor's protocol ID
- U54AR056953
- Other IDs
- U54AR056953
- Status last verified
- Jan 2015
- First submitted
- 1 Apr 2009
- Last updated
- 9 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of Transvenous Limb Perfusion With Normal Saline in Human Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT00873782
- Acronym / sponsor ID
- U54AR056953
- Conditions
- Muscular Dystrophies, Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Limb-Girdle Muscular Dystrophy
- Keywords
- Limb Perfusion, Gene Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), University of North Carolina
- Study start
- Mar 2009
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 2 Apr 2009 (estimated)
- Results
- Posted 9 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: Retrograde high pressure transvenous perfusion with normal salineParticipants will undergo retrograde high pressure transvenous limb perfusion with normal saline. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Retrograde high pressure transvenous perfusion with normal salineDose escalation of saline volume, infusion rate, and tourniquet pressure, as determined in a stepwise manner and by careful monitoring | Other | 1 |
Primary outcome
Muscle, Nerve, or Vascular Damage
Time frame: Measured within 2 weeks after limb perfusion procedure
Number of Participants with all of the following three: 1. Unchanged Doppler ultrasound to assess venous and arterial damage pre-and post perfusion based on report 2. 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 3. Without clinically significant changes in Quantitative muscle testing (QMT) strength assessments pre-and post perfusion:< 85% baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Muscular Dystrophies
RecruitingPhase 3
Efficacy, Safety, and Tolerability of Zeleciment Basivarsen (DYNE-101) in Participants With Myotonic Dystrophy Type 1
Myotonic Dystrophy Type 1 (DM1), DM1
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingEarly Phase 1
Safety and Dystrophin Expression of SPOT-03 in Duchenne Muscular Dystrophy (DMD) Patients
Duchenne Muscular Dystrophy (DMD)
RecruitingObservational study
Preclinical Assessment of an Engineered HMGB1 Protein as a Novel Companion Therapy for Muscular Dystrophies
LAMA2-MD (Merosin Deficient Congenital Muscular Dystrophy, MDC1A)
RecruitingPhase 2
Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William J. Powers, MD principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Retrograde high pressure transvenous perfusion with normal saline in people with Muscular Dystrophies and Duchenne Muscular Dystrophy, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle, Nerve, or Vascular Damage (time frame: Measured within 2 weeks after limb perfusion procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2015.