Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne Muscular Dystrophy Corticosteroids Infants Young Children Toddlers
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 25
Healthy volunteers: no

Brief summary:
While it has been known for many years that corticosteroid use benefits boys with Duchenne Muscular dystrophy (DMD), most clinicians do not consider treating until after age 3 or 4 years of age. The primary reason for the delay is that daily corticosteroid use has many side effects including short stature, obesity, and osteoporosis. A recent randomized blinded study of weekend oral corticosteroid use over one year showed equal improvement in strength with fewer side effects, particularly as related to growth and cushingoid changes. The investigators will test the efficacy of oral weekend corticosteroid use in infants and young boys with DMD who are under age 30 months. The investigators have demonstrated that the Bayley-III Scales of Infant development shows that infants and young boys in this age group who are untreated decline in abilities when compared to their peers. Here, in this Phase 2 historically controlled trial, the investigators will use these two measures and treat boys at five Muscular Dystrophy Association-DMD centers

Detailed description:
Objective. Determine if twice-weekly high dose oral prednisone improves gross motor development in infants and young boys with DMD. The investigators will perform a phase 2 historically controlled trial of oral twice-weekly prednisone (5mg/kg/dose on two consecutive days) in infants and young boys with DMD. Here the investigators propose to study the effect of this therapy in a multicenter trial of boys with DMD who are less than 30 months old at the baseline visit. Each boy will be followed for one year.

Aim 1. Determine if treatment improves gross motor function in infants with DMD over a 6-12-month period as measured by the Bayley-III. The Bayley-III infant score is the primary motor clinical endpoint of this therapeutic trial. Secondary outcomes include fine motor function, speech and language, and social function.

Aim 2. Determine if treatment improves the Adaptive Behavior Subtest of the Bayley-III (ABS) as scored by the infants' primary caregiver. In the study of untreated boys, the primary caregiver noted clear deficits, predominantly related to areas relevant to gross motor function. The ABS Aim 3. Determine if treatment improves performance on the North Star Ambulatory Assessment (NSAA) for those boys who are ambulatory.

Aim 4. Determine if treatment with weekly corticosteroids is tolerated and is safe in boys with DMD who are less than 30 months of age.

Objective 2. Determine if ultrasound of biceps and quadriceps using calibrated backscatter improves in infants and young boys with DMD who are treated with oral high dose weekly corticosteroids. Preliminary data of ultrasound imaging in infants and young boys with DMD demonstrate progressive structural damage as measured by calibrated backscatter. The ultrasound studies will be limited to the infants and boys who will enroll at the primary site (Washington University) where Dr. Craig Zaidman has the equipment and expertise to accomplish this aim.

Objective 3. Determine if caregiver burden changes with treatment of infants and young boys with DMD. Preliminary data from questionnaires suggests the caregiver burden for the primary caregiver of untreated infant and young boys with DMD is minimal. Assessment of this with in this trial will allow us to discern if this changes with a therapeutic trial.

Arms:
arm 1: Oral Prednisolone 5mg/kg/ day on two consecutive days, Friday and Saturday with breakfast

Interventions: intervention 1: Prednisolone
Intervention descriptions: intervention 1: Prednisolone (5mg per kg) will be taken on two consecutive days, Friday and Saturday mornings each week with breakfast

Protocol document:
Prot_002.pdf: 
 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
1 
 
 
Official Title of Study: Protocol for Phase 2 Historically Controlled Trial of 
Corticosteroids in Young Boys with DMD 
 
NCT Number: NCT02167217 
 
IRB Approval Date: 10/2/2013 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
2 
 
 
 
 
 
 
 
Protocol for Phase 2 Historically Controlled Trial of 
Corticosteroids in Young Boys with DMD 
 
 
 
 
MDA grant submission Revised 5/28/2013 
 
PI: Anne M. Connolly, MD 
 
STUDY COORDINATING CENTER: Washington University School of Medicine in 
Saint Louis, 660 S. Euclid Ave Saint Louis, MO 63110 (314-362-6981) 
 
Co-Investigators: 
Jerry Mendell, MD, Nationwide Children’s Hospital 
Craig McDonald, MD, University California Davis 
Susan Iannaccone, MD, University Texas South Western 
Richard Finkel, MD, Nemours Hospital, Orlando, FL 
Statistician: 
Phillip Miller, PhD Washington University School of Medicine 
Data Management Site: 
Nationwide children’s Hospital (Benjamin Rideout) 
 
 
 
 
 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
3 
 
 
 
 
 
TABLE OF CONTENTS 
 
 
Title Page…………………………………………………………………………....page 1 
 
Table of Contents.………………………..……………………………………….page 2 
 
Protocol Signature Page…………………………………………………………page 3 
 
Introduction/Background/Rationale...........…………………………………...page 4 
 
Study Design/ Objectives…………………….……………………………....….page 6 
 
Subject selection criteria………………………………….…………….............page 8 
 
Inclusion criteria 
 
Exclusion criteria 
 
Recruitment and statistical consideration…………………………….……...page 8 
Study Procedures………………………………………………………….……....page 9 
 
Enrollment and informed consent 
 
Study Visit description 
 
Schedule of Events 
 
Data Management Repository………………………………..………..…………page 11 
 
Technical approach to Data Transfer 
Data Management & Procedures for maintaining confidentiality………….page 11 
 
 
 
Adverse events reporting………………………………………………………....page 14 
 
 
Assessment of Risks and Benefits………………………………………….…..page 14 
 
References…………………………………………………………………….….....page 15 
 
 
 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
4 
 
PROTOCOL SIGNATURE PAGE 
 
MDA-DMD Research Network:  Phase 2 Historically Controlled Trial of 
Corticosteroids in Young Boys with DMD  
 
 
 
Instructions to the investigator: Please sign and date this signature page, print your 
name and the name of the facility in which the study will be conducted, and return a 
copy to the study coordinator at Washington University.   
 
 
 
I confirm that I have read this protocol, I understand it, and I will work according to this 
protocol and to the ethical principles stated in the latest version of the Declaration of 
Helsinki, the applicable guidelines for good clinical practices, or the applicable laws and 
regulations of the country of the study site for which I am responsible, whichever 
provides the greater protection of the individual. I will accept the monitor’s overseeing of 
the study. 
 
 
_________________________________________________________________ 
Signature of Investigator 
 
           Date 
 
__________________________________________________________________ 
Investigator’s Name  
 
Investigator Title 
 
__________________________________________________________________ 
Name of Facility 
 
Location of Facility (City, State)


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
5 
Purpose of this Trial 
The purpose of this trial is to determine if weekend oral corticosteroids improve 
development in infants and young boys with Duchenne Muscular Dystrophy (DMD). We 
will compare the development of infants and young boys with DMD who are treated with 
prednisone (10 mg/kg/week given in equal doses over two days) to the development of 
untreated DMD infants and young boys who have just completed one-year follow-up 
using the same measures.  Gross motor development, fine motor development, speech, 
language and social skills will be assessed at baseline, and after six months and twelve 
months treatment. 
 
Introduction/Background/Rationale 
  Duchenne Muscular Dystrophy is an X-linked, genetic disorder. The clinical 
picture consists of progressive proximal muscular weakness, which leads to loss of 
ambulation with subsequent loss of hand and arm function and respiratory and cardiac 
failure.  
The early careful natural history studies of boys with DMD relied on manual 
muscle testing using medical research council (MRC) testing and functional outcomes 1-
3. These outcomes have been extended to include quantitative measurements, which 
allow better inter-rater reliability for ambulatory boys and are currently used in 
multicenter trials4-8. Additional functional measures including activity monitoring are very 
useful for ambulatory boys 9.   
       However, few trials have used younger boys who are unable to be tested using 
traditional MRC or quantitative testing. Prior studies demonstrate effectively the 
“honeymoon” period in DMD when absolute function and strength may improve 1, 10.  
However, the improvement does not equal that seen in normal children, as they remain 
weak compared to their peers. A pilot study of baseline motor function in 33 young boys 
with DMD (mean age 3.4 years) shows markedly different gross motor skills from age-
matched controls using the Hammersmith Motor Ability Score 11. The same study 
showed the locomotor quotient of the Griffiths’ scales demonstrated deterioration in 
young boys with DMD 11.  This latter measurement showed a highly significant negative 
correlation with age. The Bayley infant motor scale (used from birth through 42 months), 
has been validated in dozens of studies of children with motor delay in the first years of 
life12-20.  Furthermore, it has an advantage in that clinical evaluators (CEs) can be 
trained in its use.   
 
The MDA funded DMD center network recently completed baseline assessment 
of 24 infants using the Bayley-III, the HFMSE, and the North Star Ambulatory Score to 
assess infants from age 3 months through 2.9 years.  One year follow up studies of 20 
of these children are complete.  Once ambulatory, boys were also able to complete the 
early motor skills of the North Star Ambulatory Assessment (NSAA) which has been 
validated in older boys with DMD.   
 
Here we propose to use the Bayley-III and the North Star Ambulatory as outcome 
measures in a phase 2 historically controlled trial in infants who are age 3 months 
through 30 months at enrollment in a multicenter trial using the 5 DMD-MDA funded 
sites.    
  
Imaging of muscle in DMD. Imaging of muscle as a marker of disease progression in 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
6 
DMD has been considered for some time. Marden et al demonstrated that high 
resolution MRI could distinguish boys less than age 10 who were still ambulatory 21. 
Recently, Dr. Craig Zaidman, a child neurologist at Washington University has studied 
ultrasound as a marker of disease in boys with DMD 22. Calculated muscle backscatter 
(cMB), a ultrasonic measure muscle damage increases with age, even during the 
“honeymoon period” before age 8 years when absolute strength continues to increase.  
Additional data obtained from untreated infants with DMD demonstrates that the linear 
increase in backscatter extends into the first year of life.  This suggests that ultrasound 
may be an excellent, non-invasive marker of this disease. This will form a secondary 
outcome for this study.  
 
Electronic Impedance Myography. 
Electrical Impedance Myography (EIM) is a new approach to the assessment of muscle 
and neuromuscular disease, the development of which has been spearheaded by 
Seward Rutkove at Beth Israel Deaconess Medical Center in Boston 23.  In EIM, very 
low-intensity, high-frequency electrical current is applied via surface electrodes and the 
consequent surface voltages are measured. The electrodes are non-invasive and do not 
require any special procedure to apply. Results thus far in a variety of disease contexts 
confirm that EIM is very sensitive to localized changes in muscle health and will serve 
as a new quantitative approach to monitoring disease states and responses to medical 
or rehabilitative therapies24-30.   Since the test is entirely painless, non-invasive, and 
independent of patient effort it has the potential of finding wide clinical utility.  
 
Thus, in 2006, with the funding support of the Center for Integration of Medicine with 
Innovative Technology (CIMIT), Dr. Rutkove, in collaboration with Dr. Joel Dawson in 
the Electrical Engineering and Computer Science Department of the Massachusetts 
Institute of Technology, began to develop a new handheld-system. The initial design 
was completed in late 2008 and initial data were obtained in 2009 through 2010 using 
this system. The data obtained with this handheld EIM approach were very promising, 
showing marked alterations in the data in 2 different types of disease states (neurogenic 
and myopathic) as compared to that seen in normal subjects. The devices developed by 
Convergence Medical Devices, Inc. have been used on over 60 individuals, including 
infants, and there have been no related adverse events (AEs) (serious or otherwise) to 
date. 
 
We plan to measure EIM from the surfaces overlying proximal and distal muscles of the 
arm and leg in infants during each study visit.  We will compare changes in EIM to other 
outcome measures overtime.  Examination of a muscle with EIM takes seconds.  We 
therefore anticipate being able to examine several muscles without undue burden on 
the infant subject.  Furthermore, EIM is entirely painless and requires only passive 
involvement of the infant.  We therefore do not anticipate any complications or 
discomfort from the performance of EIM on the infant. 
 
 
The physical risks to the study subjects are extremely low because the studies utilize 
electrical currents of extremely low intensity and do not produce any pain (in fact, one 
does not feel anything outside of the light pressure of the probe against the skin). The 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
7 
devices will run off regular household batteries with a maximal current output of 0.2 mA 
(rms), thus virtually ensuring no risk of electrical shock. Still, there is the risk that the 
repeated placement of electrodes could irritate or redden the skin and may feel 
somewhat uncomfortable. Although care will be taken to prevent this, some irritation is 
potentially possible.  
 
 Mental development of young DMD boys.  Cyrulnik et al demonstrated that cognitive 
delay is clearly recognized by parents 31. Hinton et al have also characterized verbal 
and memory skills in older boys with DMD 32. The earliest study of mental development 
in young boys with DMD (6 boys who were a subset of Brooke et al’s original study) was 
accomplished using the Denver developmental assessment 1 33.  However, because the 
Denver assessment does not provide a quotient it is not possible to quantify  the delays. 
Detailed work in mental development of young boys with DMD has been reported by 
Smith et al using the Griffith’s Mental Development Scales (GMDS) 34.  However, this 
scale is not available in the United States and requires administration by a psychologist.  
 
The most validated, commonly used scales of language and cognition in all infants and 
children through age six years are the Bayley scales of infant development (Bayley-III) 
(valid through 42 months) 35 and the Stanford Binet Intelligence Scale 5th ed. (ages 3 
years and up)36.  Both provide measurable quotients.  The Bayley-III has been used 
studies of children at risk for both motor and mental delays including premature infants, 
children with hypoxic ischemic injuries, children with Downs syndrome and children with 
immune deficiency12-20.  We also recently completed evaluation of 24 infants and young 
boys with DMD using the Bayley-III 
 
Treatment of children with DMD with twice weekly oral prednisone 
(10mg/kg/week) is safe and effective in improving strength in both boys with DMD 
and the mdx mouse model.  There is preclinical data demonstrating that weekly oral 
prednisone improves strength and prolongs life of the mdx mouse37, 38.  A pilot study by 
Connolly et al demonstrated a favorable side effect profile with no increased risk of 
obesity and maintenance of linear growth with improved strength and function 
compared to historical control boys with DMD who were not treated5.  The follow-up 
study, a randomized, blinded, controlled study of daily versus high dose weekly 
corticosteroids showed both were equally efficacious in improving strength and function 
in ambulatory boys with DMD39.  Here we propose to use the weekly regimen in young 
infants who would not tolerate the cumulative effects of daily corticosteroids. 
Participants will be given prednisone at their first visit and will be instructed to start 
administration of drug on the weekend. Drug will be given to them at every visit at no 
cost to them. 
 
Study objectives and Design 
 Objective 1.  Establish gross motor development as a valid outcome measure in 
young boys with DMD at the 5 MDA-DMD centers. Preliminary data show that 
average gross motor function infants and young boys with DMD declined over six and 
12 months compared to age matched peers when assessed using Bayley-III Scales of 
Infant Development (Bayley-III). Fine motor, cognitive, and language skills did not 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
8 
decline.  
Aim1a. Continue Validation of Bayley-III as an outcome measure in infants with 
DMD.  We will train/retrain Clinical Evaluators (CE’s) from the 5 MDA-DMD centers in 
this assessment tool.  
Aim1b. Continue validation of the North Star Ambulatory Assessment (NSAA) in 
the youngest ambulatory boys with DMD. We will train/retrain CE’s from the 5 MDA-
DMD centers in this assessment tool.  
Aim 1c.  Establish age of independent walking as a valid outcome in infants with 
DMD.  The precise age of walking for young boys with DMD has not been established in 
a prospective fashion.  For those children already walking we will ask for the age at 
independent walking defined as 10 independent steps. For those who are not yet 
walking, we will prospectively capture this information in this study. 
 
Objective 2. Determine if twice-weekly high dose oral prednisone improves gross 
motor development in infants and young boys with DMD.  We will perform a phase 
2 historically controlled trial of oral twice-weekly prednisone (5mg/kg/dose on two 
consecutive days) in infants and young boys with DMD. Here we propose to study the 
effect of this therapy in a multicenter trial of boys with DMD who are less than 30 
months old at the baseline visit.  Each boy will be followed for one year.  
Aim2a. Determine if treatment improves gross motor function in infants with DMD 
over a 6-12-month period as measured by the Bayley-III. The Bayley-III infant score 
is the primary motor clinical endpoint of this therapeutic trial. Secondary outcomes 
include fine motor function, speech and language, and social function. 
Aim 2b.  Determine if treatment improves the Adaptive Behavior Subtest of the 
Bayley-III (ABS) as scored by the infants’ primary caregiver. In the study of 
untreated boys, the primary caregiver noted clear deficits, predominantly related to 
areas relevant to gross motor function. The ABS 
Aim 2c.  Determine if treatment improves performance on the NSAA for those 
boys who are ambulatory. 
Aim 2d. Determine if treatment with weekly corticosteroids is tolerated and is safe in 
boys with DMD who are less than 30 months of age. 
 
Objective 3. Determine if ultrasound or Electronic impedance Myography (EIM)of 
biceps and quadriceps improves in infants and young boys with DMD who are 
treated with oral high dose weekly corticosteroids 3A. Determine if ultrasound 
using calibrated backscatter improves in infants and young boys treated with 
DMD. Preliminary data of ultrasound imaging in infants and young boys with DMD 
demonstrate progressive structural damage as measured by calibrated backscatter. The 
ultrasound studies will be limited to the infants and boys who will enroll at the primary 
site (Washington University) where Dr. Craig Zaidman has the equipment and expertise 
to accomplish this aim.  3B. EIM is a new approach for the assessment of muscle and 
has been shown to distinguish normal muscle from diseased muscle.  EIM is a very low-
intensity high-frequency electrical current is applied via surface electrodes and the 
consequent surface voltages are measured. The electrodes are non-invasive and do not 
require any special procedure to apply. 
 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
9 
Objective 4.  Determine if caregiver burden changes with treatment of infants and 
young boys with DMD.   Preliminary data from questionnaires suggests the caregiver 
burden for the primary caregiver of untreated infant and young boys with DMD is 
minimal.  Assessment of this with in this trial will allow us to discern if this changes with 
a therapeutic trial.   
 
Subject selection criteria 
 
Inclusion Criteria  
Clinical Diagnosis of Duchenne Muscular Dystrophy.  This must be confirmed in one of 
two ways 
1. Appropriate degree of weakness for age, creatine kinase >20X the upper limit 
of normal, and genetic mutation known to be causative for DMD.   
2. Appropriate degree of weakness for age, creatine kinase >20X the upper limit 
of normal and genetic or biopsy confirmation of Duchenne muscular 
dystrophy in a primary relative (e.g. brother or maternal uncle) 
3. De-identified, genetic studies will be reviewed by collaborator Kevin Flanigan 
prior to enrollment of subjects. 
4. Age at entry: one month through 30 months 
 
Exclusion Criteria  
Glucocorticoid treatment 
 
Recruitment of infants and young boys:  We will enroll children from age 1 
month through age 30 months. Follow-up examinations will be performed 6-month and 
12 months after the baseline visit.  The specific goal would be to determine whether the 
average change in Bayley-III scores differ from the scores of the boys who are 
untreated.   A total of 25 children will be needed and we expect to follow them every 6 
months for one year.  Based on the recruitment in the study of untreated infants we 
expect to recruit these children over 15-24 months.  We are allowing for a potential drop 
out of 5 infants.   
 
 Statistical considerations and Power Calculations for current study. 
Follow-up of twenty untreated infants and young boys with DMD showed that the 
average negative change in the Bayley III gross motor scaled score over six months 
was -0.4.  If the effect size of therapy is an increase of 1.5 points on this scaled score, 
then 19 infants would be required for 95% confidence to detect a difference. If the effect 
size of corticosteroids is +2.0 points only 11 infants would be required.  We have 
chosen to enroll 24 infants, with the expectation that 4 might be lost to follow up or drop 
out of the study.  While we have calculated the effect size for six months, additional data 
in a small subset suggest there is further decline over 12 month (total average decline 
of 1.0 point in 12 boys.  The six month and 12 month follow-up of the cohort will be 
analyzed and reported to the MDA.  
 
 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
10 
Study Procedures and Visits 
The fundamental goal of this work is to determine if two reliable developmental 
assessments (Bayley-III and NSAA) in young boys with DMD will detect a change in 
gross motor function in infants and young boys treated with twice weekly oral 
prednisone.   We will follow children for one year and they will be ages 1 month through 
30 months at enrollment.  
 
There will be a total of six visits, Baseline, and at 1, 3, 6, 9, and 12 months. 
Baseline evaluation and visits at 6 and 12 months will include: 
a) History to include age of walking defined as 10 independent steps 
b) Every 6 months Vital signs including height, weight, heart rate, blood pressure  
 
Height will be assessed in two ways 
 
1. Measurement of supine length if child is not able to stand 
 
 
2. Standing height if child is able to stand 
c) Every 6 months the following will be performed  
 
1. Bayley-III Scales of Infant Development.  
This test consists of a standardized assessment of cognitive, language, and motor 
using small toys, blocks and books.  For infants there is a special set of activities to 
assess the muscle function called Bayley-III infant motor scale which has both a 
fine motor and gross motor component. This assesses the degree of body control, 
large muscle coordination, finer skills of the hands and fingers, dynamic 
movements. This will be done through observations and questions. The Bayley-III 
infant mental scales will test language and cognition.  
 
2. North Star Ambulatory assessment North Star Ambulatory Assessment 
(NSAA).  The NSAA 40, 41 assesses functional activities including standing, getting 
up from the floor, negotiating steps, hopping, and running. The assessment is 
based on a 3 point rating scale of 2= ability to perform the test normally, 1= 
Modified method or assistance to perform test, 0=unable to perform the test. Thus, 
total score can range from 0 (completely non-ambulant) to 34 (no impairment on 
these assessments). 
 
3.Ultrasound of the muscle  (this measure will be followed only on infants 
recruited from the Washington University Site) 
This will be done by keeping the ultrasound probe on biceps and quadriceps to see 
the image of the muscle for structural changes. As the muscle changes the 
ultrasound will reflect the changes. 
 
4. EIM of Muscle.  This will be performed at all sites 
 
5. Behavior:  The Adaptive Behavior Assessment Scale (ABAS) is a well-validated 
measure of adaptive behavior and will be tested every 6 months. 
 
6. Caregiver Burden:  This will be tested by filling out the Caregiver stress 
questionnaire.  


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
11 
  
7. Complete Physical Examination and Neurological examination 
The Visits at 1, 3, and 9 months will be safety visits which can be performed locally or 
on site.  If laboratory studies are performed locally, phone visit will occur. 
 
Table 1. Schedule of Events 
Study Period (+-7 days) 
Month 
0 
 
Month 
1* 
Month 
3* 
Month 
6 
Month 
9* 
Month  
12 
Informed consent 
X 
 
 
 
 
 
Vital signs, Height, 
Weight, Occipital 
Frontal Circumference 
BMI (kg/m2) 
X 
 
 
X 
 
X 
Medical History 
X 
X 
X 
X 
X 
X 
Medication review 
X 
X 
X 
X 
X 
X 
Con Medication review 
X 
X 
X 
X 
X 
X 
Medical Events 
 
X 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
Physical examination 
X 
 
 
X 
 
X 
Neurological 
Examination 
X 
 
 
X 
 
X 
Electronic Impedance 
Myography 
X 
 
 
X 
 
X 
Ultrasound for WU 
infants only 
X 
 
 
X 
 
X 
North Star Ambulatory 
Assessment 
X 
 
 
X 
 
X 
 Bayley-III Scales of 
Infant development 
X 
 
 
X 
 
X 
 Adaptive Behavior 
Assessment Scale 
X 
 
 
X 
 
X 
Care giver Burden 
assessment 
X 
 
 
 
 
X 
CBC/Diff 
X 
X 
X 
X 
X 
X 
CPK 
X 
X 
X 
X 
X 
X 
Sodium 
X 
X 
X 
X 
X 
X 
Potassium 
X 
X 
X 
X 
X 
X 
Chloride 
X 
X 
X 
X 
X 
X 
CO2 
X 
X 
X 
X 
X 
X 
BUN 
X 
X 
X 
X 
X 
X 
Fasting Serum Glucose 
X 
X 
X 
X 
X 
X 
**Phone call or on site assessments will take place at visits 1, 3, and 9 months. 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
12 
Criteria for dose reduction: 
Prednisone dose will be reduced for 
1) An increase in Body mass index (BMI) (kg/m2) greater than 10% over 6 months 
2) A fasting blood sugar greater than 100mg/dl after dietary modification 
3) An increase in diastolic blood pressure greater than 10mm Hg over upper limit of 
normal for age 
4) An increase in systolic blood pressure greater than 15mm Hg since the last visit  
5) Otherwise, non-manageable side effects including irritability or difficulty sleeping. 
 
Data Management Repository 
The informatics component of the proposed specific aims will provide a centralized data 
management repository.  The system will provide a secure web-based application 
designed to harmonize data from the all-participating institutions.  The functionality of 
the system will include data entry, data integration, data validation and quality control, 
searching, reporting, and exporting.  The system will have three core components to 
include administration, institution, and investigator data requests.  The administration 
component will allow a defined member of the MDA DMD CRC Network access to data 
generated from their sites and data from the network at large, upon validation that data 
request forms are from participating institutions.  The approval process will be defined in 
the Manual of Operations.  Once approved, the data set is generated and released to 
that approved investigator.  The data that will be submitted to the central data 
management repository will include the following information. 
 
1) Demographics 
ID# 
Date of Birth 
Date of study visit 
DMD Gene Mutation  
 
Age (derived from DOB, Date of study) 
Height/Length in centimeters 
Weight in kilograms 
Body Mass Index  
Occipital Frontal Circumference in centimeters 
 
2) Assessments 
a) Bayley-III scales of Infant Development 
b) North Star Ambulatory Assessment 
c) Adaptive Behavior Assessment Scale (ABAS) 
d) Caregiver Burden 
3) History including Dietary history recorded 
4) Medical events recorded 
5) Adverse events recorded 
6) Concomitant medications recorded 
 
Time expected to complete these visits will vary somewhat depending on the 
subjects’ own strength and function.  The predicted time to complete all procedures and 


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
13 
questionnaires is 2-3 hours. 
 
Data Management  
A centralized data management repository will be used for this study.  The system will 
provide a secure web-based application designed to harmonize data from all 
participating institutions.  The functionality of the system will include data entry, data 
integration, data validation and quality control, searching, reporting, and exporting.  The 
system will have three core components to include components to include 
administration, institution, and investigator data requests.  The administration 
component will allow a defined member of the MDA DMD CRC Network access to data 
generated from their sites and data from the network at large, upon validation that data 
request forms are from participating institutions.  The approval process will be defined in 
the Manual of Operations.  Once approved, the data set is generated and released to 
that approved investigator. 
 
Procedures for maintaining confidentiality  
Institutions participating in the DMD Clinical Outcomes Project including Washington 
University in Saint Louis, Nationwide Children’s Hospital in Columbus Ohio, University 
Texas Southwestern, Nemours Children’s Hospital, Orlando Florida, and University of 
California Davis will collect the necessary data as defined in the Manual of Operations.  
Patients and the supporting data will be de-identified at each given site using a defined 
identifier schema satisfying HIPAA requirements prior to submitting study data to the 
informatics Core.  As each case is being completed the participating institution will 
securely submit to the data center the case report forms utilizing a secure file transfer 
protocol (SFTP) incorporating technology providing encrypted channels, preventing 
passwords and sensitive information from being transmitted via the Internet. 
 
Adverse events reporting: 
Adverse events in this trial to validate outcomes will be reviewed within 24 hours by the 
PI at each site who will be responsible for reporting such events and communicating 
those events to the primary PI, Dr. Anne Connolly (314-362-6981 Work) or 314-581-
9948 (Cell phone). 
 
Assessment of Risks  
Risks of oral weekly Prednisone 
Likely: Mild irritability or sleep disturbance on the days prednisone is taken. Some 
children may experience increased hunger on the days prednisone is taken 
Less Likely: Corticosteroid use may decrease the immune response.  With intermittent 
use proposed in this study, this risk is less common. Some children may develop 
stomach pain or discomfort. Some children may develop excessive weight gain 
Rare:  Rarely, children may develop intestinal bleeding. Rarely, children may develop 
adrenal suppression.  While this is common in children taking daily corticosteroids it is 
rare with the weekend dosing regimen.  This will be tested for with safety laboratory 
tests at baseline, 1, 3, 6, 9, and 12 months. 
  


 Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys with DMD             
 
14 
 Risks of Muscle Testing. 
 Likely:  Muscle fatigue. 
 Less likely: None Known. 
 Rare: None Known. 
 
Risks of Language and Cognitive Assessments: 
Likely: Some children may feel uncomfortable with the evaluator. 
Less Likely: None Known. 
Rare: None Known. 
 
Risk of Ultrasound of muscle: 
Likely: Irritation or rash at the probe site. 
Less Likely: None Known. 
Rare:  None Known. 
 
Risk of Electronic Impedance myography: 
Likely: Irritation or rash at the probe site. 
Less Likely: None Known. 
Rare:  None Known. 
 
Risk of Blood Draws: 
Likely: Bruising at site 
Less likely: Fainting 
Rare: Local infection 
 
Patients may experience all or some of the risks listed above. There may also be 
unknown risks. The PI will be responsible for any questions subjects have about these 
risks.  
 
Assessment of Benefits 
There is abundant evidence in older children that oral corticosteroids improve 
strength and function.  There is also emerging evidence that those treated early 
with corticosteroids may have benefits many years later with prolonged walking.  
The direct benefit may be improvement in motor development.  There may also 
be an improvement in behavior as this was also seen in the randomized trial of 
daily versus weekly corticosteroids. It is hoped that the knowledge gained from 
this study will help us know if this group of infants can be reliable subjects in other 
clinical trials.   
 
Decision to discontinue treatment 
If the family decides to discontinue corticosteroid therapy they will be given the 
option to continue to be followed using the same clinical outcomes described 
above.  


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15 
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SAP_000.pdf: 
Statistical plan for  
Historically Controlled Trial of Corticosteroids in Young Boys With 
Duchenne Muscular Dystrophy 
 
 
Statistics will be performed with Excel (Microsoft Inc.) and GraphPad 
Prism (GraphPad Software, La Jolla, CA). P-values will all 2-tailed.  A p 
value of <0.05 will interpreted as showing statistical significance. Mann 
Whitney U will be used for non-parametric data.   
Analysis of data will be performed in two ways.  First, the change 
over one year in the Treated Cohort will be compared to the previously 
published Historical Control Cohort (HCC).  Second, repeated measures 
(paired t- tests) were used to analyze each boy’s performance over his own 
baseline.