DMD: Which Steroid Regimen Is Best?

Prednisone and other drugs in the corticosteroid family have become standard treatment for Duchenne muscular dystrophy (DMD) in much of the world for almost a decade. In this disorder, they slow the decline of muscle function and prolong walking ability. However, corticosteroids have significant side effects, such as weight gain, bone loss, cataracts and behavior changes.

Many questions about corticosteroid use in DMD remain, particularly about which medication, which dosage regimen, and what duration of treatment should be prescribed to maximize benefit and minimize harmful effects.

Now, with the support of the National Institute of Neurological Disorders and Stroke (NINDS), the first four sites in a 40-center, multinational trial exploring these questions have begun enrolling participants. More centers will open as they are ready.

300 boys on three regimens

In the phase 3 trial, investigators at medical centers in the United States, Canada, the United Kingdom, Germany and Italy will study young boys with DMD for five years.

Each participant will be assigned to receive one of three corticosteroid regimens for three to five years:

• daily prednisone at 0.75 milligrams per kilogram of body weight;
• intermittent prednisone — alternating 10 days on and 10 days off — at 0.75 milligrams per kilogram of body weight; or
• daily deflazacort at 0.9 milligrams per kilogram of body weight.

Prospective participants must:

• be male and have a confirmed diagnosis of DMD;
• be 4 to 7 years old;
• be able to rise from the floor independently; and
• be willing and able to comply with scheduled visits, drug administration plans and study procedures, including being able to maintain reproducible respiratory measurements.

Prospective participants must not:

• be undergoing or have had previous treatment with more than four consecutive weeks of oral corticosteroid therapy or other immunosuppressive medications;
• have a history of major kidney or liver impairment, immune abnormalities or other contraindications to corticosteroid therapy;
• have a history of chronic systemic fungal or viral infections;
• have diabetes;
• lack immunity to chickenpox;
• have symptomatic cardiac abnormalities;
• have severe behavioral problems;
• weigh less than 13 kilograms (about 29 pounds); or
• have any previous or current medical condition, physical findings or laboratory abnormalities that could affect a child's safety, make it unlikely that treatment will be completed, or impair the assessment of study results, in the judgment of the site investigator.

The principal investigators are neurologist Robert Griggs at the University of Rochester Medical Center in New York and geneticist Kate Bushby at the Institute of Human Genetics in Newcastle Upon Tyne in the United Kingdom.

To participate

For details, including contact information and recruitment status (open or not yet open) for the study sites, see Finding the Optimum Regimen for Duchenne Muscular Dystrophy (FOR-DMD) (or enter NCT01603407 in the search box at ClinicalTrials.gov).

For general information about U.S. sites, contact Kimberly Hart, U.S. project manager for FOR-DMD in Rochester, N.Y., at (585) 275-3767 or kim_hart@urmc.rochester.edu.

The four sites that are currently open to recruitment are in Los Angeles; Rochester, N.Y.; Calgary, Alberta, Canada; and Newcastle Upon Tyne, United Kingdom.

Site-specific study coordinators at open sites follow.

California
Angel Hu
University of California,Los Angeles
Los Angeles
(858) 228-0461
angelhu@mednet.ucla.edu

New York
Debra Guntrum
University of Rochester Medical Center
Rochester
(585) 275-6374
Debra_Guntrum@urmc.rochester.edu

Canada
Caitlin Wright
Alberta Children's Hospital
Calgary, Alberta
(403) 955-3192
Caitlin.Wright@albertahealthservices.ca

United Kingdom
Becky Davis
Institute of Human Genetics
International Centre for Life
Newcastle Upon Tyne
0191 241 8649
Becky.Davis@newcastle.ac.uk

For more information

To learn more about corticosteroids and DMD, see:

• New DMD Care Recommendations Released (summary of care guidelines for DMD released by the Centers for Disease Control and Prevention, with a link to the scientific papers from which it is derived, Quest, Dec. 31, 2009); and
• Charting a Corticosteroid Course: The Benefits and Side Effects of Prednisone and Deflazacort (multipart feature story on the details of corticosteroid treatment's benefits and risks, Quest, May 1, 2007).