MDA Funds Study of Prednisone in Very Young Boys with DMD

Pediatric neurologist Anne Connolly has received an MDA grant to study the effects of prednisone on Duchenne muscular dystrophy in very young children.

MDA has awarded a grant to Anne Connolly, a pediatric neurologist at Washington University in St. Louis, to conduct a trial of prednisone in very young boys with Duchenne muscular dystrophy (DMD). Connolly will conduct this phase 2 trial through the five centers that make up the MDA Duchenne Clinical Research Network.

The $343,787 grant began Aug. 1, 2013, and runs through April 30, 2016.

"This is a very important study for at least two reasons," said Jane Larkindale, MDA's vice president of research.

"First, there are no data currently supporting whether early use of corticosteroids is beneficial to DMD patients or whether there could be detrimental effects. This study will determine if corticosteroids should be administered soon after diagnosis in young patients.

“Second, the study will allow the outcome measures for young DMD patients that were recently developed with MDA support to be tested in a therapeutic trial, potentially opening up future trials to these young patients."

More information needed on steroids in DMD

Corticosteroid medications — mainly prednisone and the related drug deflazacort — have been standard treatments for DMD for several years and are recommended by the American Academy of Neurology (AAN). However, many questions remain about the details of their administration, including the age at which they should be started.

Although the original recommendation by the AAN was for 0.75 milligrams of prednisone per kilogram of body weight to be given daily, other dosing regimens have been suggested and are recommended by some practitioners as a way to maximize the benefits of corticosteroids and minimize side effects.

An MDA-supported study published in July 2011 found that 10 milligrams per kilogram of prednisone per kilogram of body weight per week, given only on weekends, provided the same benefits and side-effect profile as daily prednisone. This is the regimen that Connolly plans to use in the forthcoming trial, as it may be easier for young children to tolerate than daily corticosteroids.

Earlier diagnosis, functional measurements now possible

Until recently, treatment with prednisone or other corticosteroids in DMD rarely has been initiated prior to age 4 or 5.

In part, that's because the disease is rarely diagnosed before age 3 or 4, when weakness becomes obvious. Another reason is that, until now, there have not been reliable ways to measure subtle changes in function in very young children with DMD.

Now, however, there is increased interest in diagnosing DMD much earlier, such as through newborn screening for the disorder, and in investigating the benefits and risks of treating the disease much earlier.

There also have been successful efforts to determine how to measure motor, cognitive and behavioral function in very young DMD patients. As a critical first step toward clinical trials in very young boys with DMD, MDA's DMD Clinical Research Network conducted a study to validate outcome measures for DMD-affected children younger than age 3.

The study, conducted by Anne Connolly and colleagues and published in May 2013, found that specific testing can measure motor, cognitive and language functions in very young children with DMD, and that these functions in DMD-affected children are different from those in unaffected children at an earlier age than previously thought.

About the trial

The new MDA-funded trial — which is not yet open for recruitment — will treat 25 boys with a confirmed DMD diagnosis who are between 1 month and 30 months (2½ years) old with weekend-only prednisone and compare their outcome measures with data about untreated boys with DMD of the same age ("historical" controls).

Using outcome measures validated in the previous MDA-supported study (the Bayley III and the North Star Ambulatory Assessment), the investigators will compare the development of infants and young children with DMD treated with prednisone (given at 10 milligrams per kilogram of body weight per week given in equal doses over two days) to the historical control group, using the same measures.

The outcome measures will assess:

  • gross motor development (activities such as sitting, crawling and walking);
  • fine motor development (activities such as eating with utensils or stacking blocks);
  • speech and language development; and
  • social skills.

Additional assessments include seeking caregivers' perspectives on the difficulties of caring for young children with DMD; imaging of muscles; and noninvasive electrical studies of muscle activity.

The participants will be assessed when they begin the study, after six months and after one year.

The study will take place at the five centers in the MDA Duchenne Clinical Research Network, which include the following:

  • University of California, Davis;
  • Nemours Children's Hospital, Orlando, Fla.;
  • Washington University, St. Louis, Mo.;
  • Nationwide Children's Hospital, Columbus, Ohio; and
  • Children's Medical Center, Dallas.

Details on how to participate in this study will be made available as soon as they are known.

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