April 2008

Results of this multicenter study conducted by Diana Escolar at Children’s National Medical Center in Washington, with many others at different clinics, were reported in April 2008 at the 60th annual meeting of the American Academy of Neurology.

The investigators tested pentoxifylline for a year in 17 boys with DMD who were between 4 and 9 years old and hadn’t taken corticosteroids. Of 17 patients initially enrolled, only nine completed the study. Strength measurements didn’t show a significant change during the study. Five of the eight participants who withdrew did so because of intolerable side effects, such as nausea and vomiting and reduction of white blood cell numbers.

The investigators said the lack of deterioration in strength in a year’s time suggests a possible beneficial effect on disease progression and warrants further study with a different formulation of pentoxifylline.

Pentoxifylline is a medication that, in another form, has Food and Drug Administration (FDA) approval for the treatment of obstruction of the arteries. It decreases the viscosity ("stickiness") of the blood and improves blood flow. This drug is also an anti-inflammatory drug different from steroids, and has an antifibrotic effect, meaning it decreases the formation of scar tissue.

In DMD this drug has the potential to decrease muscle breakdown through to its anti-inflammatory actions, and to lessen the formation of abnormal scar tissue ("fibrosis") that can prevent muscle regeneration. These effects have been seen in the mouse model of DMD (the mdx mouse) and in experiments on DMD muscle tissue in the laboratory. The decrease in muscle breakdown and fibrosis might result in improvement of muscle strength.

This study is for 4- to 7-year-old boys with DMD who have not taken steroids. The total duration of the trial is 15 months.

Patient eligibility will be assessed during two screening visits, where clinical history, muscle strength testing, electrocardiogram (EKG) and blood work will be done. Once the study doctors decide a child is eligible to be in the study, he will then come back once a month for three months to have his strength tested. (This is called the "lead-in period.")

After three months, participants will begin to take pentoxifylline in a liquid form. This form has not been approved by the FDA and is only investigational. The liquid form is being used because it allows the investigators to administer the exact dose per kilogram of body weight for each boy, to prevent underdosing and overdosing (with its potential associated toxicity). This study will also require a magnetic resonance imaging scan (MRI) of the leg muscles at before pentoxifylline is taken and at the end of the study.

The primary aim is to assess the safety of pentoxifylline in children with DMD. A secondary aim is to estimate strength change, if any, over time. This estimate will allow the investigators to develop a rigorous statistical plan for future studies.

Participants must

* have Duchenne muscular dystrophy (DMD)

* be between 4 and 7 years old

* never have taken steroids, such as prednisone or deflazacort