Neuromuscular Clinical Studies

The secondary objectives are to evaluate the safety and tolerability, PK, QTc effects, and impact on functional assessments of 2 different doses of GSK2402968 versus placebo over 24 weeks in ambulant subjects with DMD and to assess safety, dystrophin half-life, and persistence of efficacy during the post treatment period.

• Be diagnosed with Duchenne muscular dystrophy
• Be able to walk more than 75 meters within 6 minutes (6MWD), and to arise from the floor in less than 7 seconds
• Be on a stable dose of steroids for six months
• Have one of the following out-of-frame deletions in the DMD gene:
  exons 13-50
  exons 29-50
  exons 43-50 
  exons 45-50
  exons 47-50
  exons 48-50
  exons 49-50
  exon 50
  exon 52

Whether all children with DMD have cellular immunity to dystrophin is unknown. In some patients, immune cells may be virtually exclusive to muscle or found in such low frequency in peripheral blood that detection becomes very difficult. We intend to sample both blood and muscle to provide a much more accurate estimate of how many subjects have an immune response that will affect future gene replacement therapy.

This study requires a blood draw in order to see if patients with DMD/BMD produce an immune reaction against the nonfunctional dystrophin protein. If there is an immune response, the doctors will need to study it very precisely and may request the same amount of blood be drawn during subsequent clinic visits. Patients can say yes or no to these extra blood draws.

Depending on the blood test results, patients may also be asked to have a muscle biopsy. The cells from muscle tissue will then be tested to measure the immune response. An open biopsy is usually performed on the upper thigh, although in some cases other muscles may be targeted. The muscle biopsy may be performed under local anesthetic (in patients 13 years old and older) or under conscious sedation. Patients must sign a different consent form for the muscle biopsy if they chose to undergo this procedure.

The investigators seek to enroll over 60 patients with a known dystrophinopathy for the blood draw. Additionally, 30 of those patients will be asked to undergo a muscle biopsy.  

Inclusion:

• DMD and BMD patients with a confirmed DNA mutation
• There are no exclusion criteria for participation if subjects can tolerate a blood draw

Exclusion:

• For those patients undergoing a muscle biopsy, anyone with cardiomyopathy (EF <40%) or FVC <30% predicted may be excluded to avoid complications from conscious sedation during the procedure

If you would like to discuss these studies further, please contact:

Chelsea Rankin, Clinical Research Coordinator.
(614) 355-2897
Chelsea.Rankin@NationwideChildrens.org

Inclusion:

• Diagnosis of DMD
• Age 7 and up
• Non-ambulant without assistive devices for at least 1 year due to DMD

Exclusion:

• Require daytime ventilator assistance
• Any major surgical procedure within 1 month prior to start of study
• Exposure to investigational treatment other than steroids

We will test gross motor development (use of large muscle groups to perform tasks like walking, balancing, crawling) and language and cognitive development (information processing, language learning, and other aspects of brain development) as outcome measure in infants and young children with DMD.  Subjects will also undergo ultrasounds of biceps and quadriceps to provide a measure of muscle damage in dystrophic muscle.  Also a care giver assessment questionnaire will be administered at yearly intervals to primary care giver of subjects. We will enroll children from age 1 month through 3 years of age. Follow-up examinations will be performed at 6-month intervals for 2 years or through 5 years of age. A total of 6 children will be needed at Nationwide Children’s Hospital.

Inclusion Criteria:

• Confirmed dystrophinopathy in child or primary relative
• 1 month to 3 years old at enrollment

Exclusion Criteria:
Glucocorticoid treatment

Your participation will help design the tests to be performed to measure patient improvement in future clinical trials.  We will also add your information to our list of patients who you would like to be contacted about upcoming clinical trials for their specific diagnosis.

Participants must be able to walk for 6 minutes and have a documented diagnosis of:

Sporadic Inclusion Body Myositis (sIBM) or
Becker Muscular Dystrophy (BMD)

Participants will be asked to perform timed functional tests such as standing up from a chair, walking for 6 minutes, and having muscle strength tested.

Interested individuals should contact:
Linda Lowes
Linda.Lowes@NationwideChildrens.org

or

Lindsay Alfano
Lindsay.Alfano@NationwideChildrens.org

or call (614) 722-6881

Participants will have a Doppler echocardiogram when they begin the study and at least once a year or more for standard of care. Skeletal-muscle testing will be done once per year. Participants will see a cardiologist as often as needed for standard of care.

Any DMD patient who is being seen in cardiology clinic on a regular basis for heart assessment will be offered to be part of the Natural History Study.

Inclusion Criteria

• All dystrophinopathy patients (i. e. Duchenne or Becker MD patients) of all ages
• Must have identifiable dystrophin mutation
• Glucocorticoid treatment acceptable
• Ongoing treatment with cardiac medications is acceptable

Exclusion Criteria

• Inability to obtain patient cooperation for Doppler-echocardiogram

Study Doctors

• Kevin M. Flanigan, MD
• Jerry R.Mendell, MD

Contacts
For either study, contact the site nearest you.
 
Ohio
Laurence Viollet
Nationwide Children's Hospital
Columbus
laurence.viollet@nationwidechildrens.org

California
Erica Goude
University of California-Davis Medical Center
Sacramento
erica.goude@ucdmc.ucdavis.edu
 
Massachusetts
Gretchen DeLuke
Children's Hospital Boston
gretchen.deluke@childrens.harvard.edu
 
Minnesota
Amy Erickson
University of Minnesota Medical Center
Minneapolis
eric1820@umn.edu

Missouri
Cheryl Rainey
Washington University Medical Center
St. Louis
rainey_c@kids.wustl.edu

Study requirements include providing a blood sample for dystrophin gene mutation analysis, and visiting one of the participating centers for a yearly examination.  Mutation testing is performed at no cost to the patient by collaborators at the University of Utah Genome Center, and patients receive a copy of their genetic testing results.

Participating centers include:

• Nationwide Children’s Hospital, Columbus, OH
• Washington University, St. Louis, MO
• University of Utah, Salt Lake City, UT
• University of Iowa, Iowa City, IA
• Children’s Hospital of Philadelphia, Philadelphia, PA
• University of Minnesota, Minneapolis, MN
• University of California, Davis, Sacramento, CA

Additional information is available at www.dystrophin.org

Study Doctors

·         Kevin M. Flanigan, MD

·         Jerry R.Mendell, MD

Coordinator
Chelsea Rankin
(614) 355-2897