DISEASE CLASSIFICATION(S):
Duchenne Muscular Dystrophy(DMD)
NAME OF CLINICAL TRIAL/STUDY:
Prednisone - A Randomized Study of Daily Versus High-Dose, Weekly Therapy in DMD
TRIAL RESULTS:
May 2009
Additional results from this study were reported at the 2009 meeting of the American Academy of Neurology, held in Seattle April 25-May2.
A somewhat surprising result about moderate-dose, daily prednisone versus high-dose, weekend-only prednisone in boys with DMDwas obtained by a team of researchers from Children's National Medical Center in Washington (CNMC) and the University of Pittsburgh.
The investigators found behavioral side effects associated with prednisone lessened over the course of a year in the daily prednisone group but stayed the same in the weekends-only prednisone group.
Twenty-eight boys with DMD were randomly assigned to receive 0.75 milligrams per kilogram of body weight of prednisone daily, while another 28 were randomly assigned to receive 10 milligrams per kilogram of prednisone weekluy over two consecutive days (the weekend).
The investigators administered the Child Behavior Checklist (CBCL) rating scale at screening and after one, three, six, nine and 12 months.
Total behavioral problems at the start of the study were similar between the two treatment groups. One month into treatment, there were no changes in behavior within the weekend prednisone group and an improvement in total problems and attention in the daily prednisone group.
After a year, there were no significant differences within the weekend group. However, in the daily prednisone group, there were significant decreases in total problems, such as attention and aggression. The daily group also showed significantly fewer behavioral problems than the weekend group at one year.
April 2008
Two days a week of the corticosteroid prednisone at a high dose appears to be almost as beneficial as a daily moderate dose of the drug in boys with DMD, and some side effects may be less severe, investigators reported in April 2008 at the 60th annual meeting of the American Academy of Neurology.
The year-long, multicenter study, supported by MDA and the National Institutes of Health, was conducted by Diana Escolar at Children’s National Medical Center in Washington, with colleagues at many institutions.
The investigators analyzed data from 64 boys with DMD who were 4 to 10 years old, had not previously taken corticosteroids, and were still walking.
The boys were randomly assigned to take prednisone at 0.75 milligrams per kilogram every day, or to take prednisone at 10 milligrams per kilogram per day two days a week. Neither the boys nor the investigators knew who was on which schedule. (Boys on the two-day prednisone schedule received “dummy” pills on the no-prednisone days.)
Effects on strength maintenance were similar in the two groups, but time required to get up from the floor was better in the daily prednisone group.
Growth retardation, a known prednisone side effect, was less severe in the two-day, high-dose prednisone group, but weight gain, another serious side effect, was the same in both groups after a year.
TRIAL UPDATES:
March 2008
According to principal investigator Diana Escolar, M.D., this study was completed as of February 2008. Dr. Escolar intends to announce results at the 60th annual meeting of the American Academy of Neurology, to be held in Chicago April 12-19, 2008.
October 2004
The trial has been redefined once more to include "blinding." Blinding means the actual treatment given is not known. This prevents bias in the results and is the most scientifically valid way to conduct studies. The trial has been "double-blinded," which means neither the investigators nor the patients will know what treatment is actually given to each participant.
April 2004
This trial had to be redesigned because of new findings regarding the “natural history” of the disease. These findings revealed that boys under the age of 7 may respond differently to treatment from boys 7 and older, and that there may be minimal or no deterioration in strength, as measured by manual muscle testing, in DMD-affected children ages 10 and under over a six-month period. As of spring 2004, it has opened, with a larger target number of participants.
PURPOSE AND RATIONALE:
This trial is to test the effectiveness of a high-dose, weekend-only regimen of the corticosteroid prednisone in Duchenne muscular dystrophy (DMD) as compared to the standard, moderate-dose, daily regimen that is commonly used in this disease.
The investigators say that results of a recent, open-label, pilot study of the high-dose, weekend prednisone therapy suggest that the new regimen is as effective as daily prednisone but with fewer and less severe side effects. Most other alternative schedules to daily prednisone, they say, have been less effective than daily prednisone.
The primary aim of this study will be to measure the ability of prednisone to increase muscle strength in boys in both treatment groups. This is a measure of effectiveness (efficacy). In addition, the investigators will compare side effect rates between the two groups, since they believe that side effects of the new regimen will likely be less severe. This is a measure of safety.
STUDY DETAILS:
The study is a randomized trial, double-blind trial, meaning participants will have a 50-50 chance of being assigned to receive either the standard, daily treatment or the high-dose, weekend treatment, and that neither parents, patients nor investigators will know which treatment each child is receiving. In case of an emergency, the patient’s treatment status can be "unblinded" by the pharmacist, so that proper therapy can ensue.
The study will last 15 months. Participants must visit one of the participating centers monthly for three months and then every three months for the remainder of the study. The first and last visits will include two days of strength testing, which must be repeated within one week.Through assistance from Mercy Medical Airlift, the investigators may be able to arrange subsidized or free air travel for study participants who are U.S. residents and more than 200 miles away from a study site. Some temporary housing may be provided during study visits through participating Ronald McDonald House charities.
OPENING DATES:
Nov 15 2003
CLOSING DATES:
Dec 1 2005
TARGET NUMBER OF PARTICIPANTS:
140
RECRUITMENT STATUS:
Open
ELIGIBILITY REQUIREMENTS:
Inclusion criteria:
- ages 4 to 10 years
- able to walk without assistance
- diagnosis of DMD confirmed by at least one of the following:
- dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, or;
- dystrophin gene deletion test showing one or more exons missing in the central rod domain (exons 25-60) of the dystrophin gene, with reading frame predicted to be "out-of-frame" and clinical picture consistent with typical DMD, or;
- test involving complete sequencing of the dystrophin gene showing a point mutation, duplication or other alteration in the dystrophin gene sequence resulting and a clinical picture consistent with DMD
- never exposed to corticosteroids
- evidence of muscle weakness by Medical Research Council (MRC) score or clinical functional evaluation (this will be tested during screening)
- ability to provide reproducible repeat quantitative muscle testing (QMT) biceps score within 10 percent of first assessment score (this will be tested during screening)
- ability to swallow tablets
Exclusion Criteria:
- failure to achieve one or more of the diagnostic inclusion criteria noted above
- symptomatic DMD carrier
- use of carnitine, creatine, glutamine, coenzyme Q10, amino acids or any herbal medicines within the last three months
- history of significant other illness or significant impairment of kidney or liver function, or other contraindication to corticosteroid therapy
- positive protein purified derivative (PPD) test, indicating exposure to tuberculosis
- lack of prior exposure to chickenpox
- carrier of oral herpes simplex virus
- evidence of significant heart disease (will be checked during screening)
