Once Weekly Infant Corticosteroid Trial for DMD

Sponsor

Anne M. Connolly (Other)

Overall Status

Recruiting

CT.gov ID

NCT05412394

Collaborator

Ann & Robert H Lurie Children's Hospital of Chicago (Other), Children's Hospital Medical Center, Cincinnati (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The hypothesis tested here is that a lower dose of intermittent oral corticosteroids (5mg/kg/week) will be equally effective to the 10mg/kg/week dose.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: Prednisolone	Phase 4

Detailed Description

The investigators know that the muscle destruction from Duchenne muscular dystrophy (DMD) begins in infancy and we previously demonstrated that motor decline in infancy compared to typically developing infants reflects that destruction. Because of the known side effects of daily corticosteroids, most physicians do not begin treatment until age 3-5 years. Most side effects (Cushingoid faces, linear growth arrest, and bone density loss) did not happen in infants and in ambulatory boys in two separate studies. However, in infants and young boys taking (10mg/kg/week), 56% of infants and young boys did have an increase in weight percentile compared to baseline. This study will test this lower dose of prednisolone (5mg/kg/week) in an unblinded study in infants and young DMD boys (ages 1 through 30 months) to determine if equal efficacy can be achieved with fewer side effects. The primary outcome for this study will be gross motor function. The study team will enroll boys from age 1 month through 30 months and follow each for two years. We will assess gross motor function using three outcome measures: the Bayley-4 Scales of Infant and Toddler Development (Bayley-4) and the newly developed Neuromuscular Gross Motor Outcomes (GRO) and the NorthStar Ambulatory Assessment (NSAA). The one-year outcome will be the change in the Bayley-4 Scaled Score and the two-year outcome will be the change in the GRO score. This study will determine if a lower dose is equally effective and if that dose may lessen the weight gain seen in about half of the infants in the first study. Both the Bayley-4 and the GRO allow assessment of gross motor function and are feasible in all boys with DMD under the age of 42 months. In addition, the GRO allows continued assessment of motor function across a wide age span which will allow this cohort to be followed for two full years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase-2 Trial of 5mg/kg/Week Prednisolone in Young Boys With DMD

Actual Study Start Date :

Apr 30, 2021

Anticipated Primary Completion Date :

Aug 30, 2024

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental This is a one-arm study and the group of subjects are all experimental and will receive drug.	Drug: Prednisolone Liquid, 5mg/kg per week, for one year Other Names: Corticosteroid

Arm

Intervention/Treatment

Experimental: Experimental

This is a one-arm study and the group of subjects are all experimental and will receive drug.

Drug: Prednisolone

Liquid, 5mg/kg per week, for one year

Other Names:

Corticosteroid

Outcome Measures

Primary Outcome Measures

The change from baseline to 24 months for the Gross Motor Scaled Score. [Baseline visit to 24 month visit]
Neuromuscular Gross Motor Outcome (GRO): The Neuromuscular GRO is a gross motor outcome measure developed to assess whole body strength, motor development, and function for all levels of ability across the lifespan in those diagnosed with neuromuscular disease. Items are administered following the developmental sequence, as appropriate for age and ability. Maximum score is 100 points.

Secondary Outcome Measures

Language (expressive and receptive), Social and Fine Motor skills at 24 months as assessed by the Bayley-4 Scales of Infant and Toddler Development [Baseline visit to 24 month visit]
The Bayley Scales of Infant and Toddler Development (Bayley-4) are recognized internationally as a comprehensive tool to assess children from as young as 15 days old. With Bayley-4, it is possible to obtain detailed information from non-verbal children as to their functioning. Children are assessed in the five key developmental domains of cognition, language (receptive and expressive), & motor (fine and gross).
Linear growth [Baseline visit to 24 month visit]
We have previously shown that all infants and young children treated with 10mg/kg/week did maintain their linear growth. This protocol is designed to determine also if the lower dose will still maintain benefit.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 30 Months

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects ages 1 month through 30 months
Weakness consistent with Duchenne on exam, creatine kinase ≥ 20 times the upper limit of normal, and genetic mutation known to be causative for DMD.