Duchenne Muscular Dystrophy
Conditions
Keywords
DMD, Duchenne Muscular Dystrophy, Insulin like growth factor, 6 minute walk test
Brief summary
The purpose of this study is to determine whether IGF-1 therapy improves or preserves muscle function in Duchenne Muscular Dystrophy (DMD).
Detailed description
Detailed Description: DMD is a progressive degenerative muscle disorder for which there is no current cure. Glucocorticoids (GC) are often used to improve motor function and survival but have significant side effects such as growth failure, weight gain, insulin resistance and osteoporosis. IGF-1 stimulates both the proliferation and differentiation of skeletal muscle cells and is thus important for muscle repair and regeneration. IGF-1 offers potential as a therapeutic agent for DMD as it may improve or preserve motor function and reduce GC side effects such as growth failure and insulin resistance.
Interventions
DRUGIGF-1
IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.
Sponsors
Ipsen
Charley's Fund
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* DMD diagnosed with mutational testing and/or complete absence of dystrophin on muscle biopsy * Proximal pelvic girdle weakness (Gower's maneuver, difficulty with arising from floor and going up steps) * Male * Age \> 5 years of age * Bone maturation (assess by bone age x-ray): \</= 11 years of age * Daily GC (prednisone or deflazacort) therapy for \> 12 months * Ambulatory * Informed consent * Willingness and ability to comply with all protocol requirements and procedures
Exclusion criteria
* Current or prior treatment with growth hormone or IGF-1 therapy * Non-ambulatory * Pubertal (based on clinical Tanner staging examination) * Congestive cardiac failure * History of intracranial hypertension * Daytime ventilatory dependence (non-invasive or tracheostomy) * Concomitant therapy - any other medications/supplements that would be considered, in the opinion of the investigators, to affect muscle function, need to have been started 3 months prior to enrollment * Patients enrolled in other clinical drug trials * Any physical or mental conditions which may, in the investigators'opinions, render the subject unable to complete the tasks of the study appropriately * There will be no selection by ethnicity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in 6-Minute Walk Distance Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | 6 months | Outcome Measure Data Table shows change of 6-Minute Walk Distance at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Height Velocity Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | 6 months | Outcome Measure Data Table shows change of height velocity at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1). |
| Difference in North Star Ambulatory Assessment (NSAA) Score Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | 6 months | Outcome Measure Data Table shows change of North Star Ambulatory Assessment (NSAA) score at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1). The NSAA is a 17-item scale that grades performance of various functional skills on a scale from 0 (unable), 1 (complete independently but with modifications), and 2 (complete without compensation). The range of NSAA score is from 0 to 34. The higher score indicates better motor function. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IGF-1 IGF-1 plus standard steroid treatment
IGF-1: IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months. | 17 |
| Standard Steroid Treatment Alone Standard daily steroid treatment for DMD | 21 |
| Total | 38 |
Baseline characteristics
| Characteristic | IGF-1 | Standard Steroid Treatment Alone | Total |
|---|---|---|---|
| Age, Continuous | 8.56 Years STANDARD_DEVIATION 1.28 | 8.70 Years STANDARD_DEVIATION 1.79 | 8.64 Years STANDARD_DEVIATION 1.67 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 17 Participants | 21 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 20 / 22 | 21 / 22 |
| serious Total, serious adverse events | 1 / 22 | 0 / 22 |
Outcome results
Primary
Difference in 6-Minute Walk Distance Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline
Outcome Measure Data Table shows change of 6-Minute Walk Distance at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1).
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IGF-1 | Difference in 6-Minute Walk Distance Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | 3.4 meters | Standard Deviation 32.4 |
| Standard Steroid Treatment Alone | Difference in 6-Minute Walk Distance Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | -5.1 meters | Standard Deviation 50.2 |
p-value: 0.5395% CI: [-37.1, 20.1]t-test, 2 sided
Secondary
Difference in Height Velocity Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline
Outcome Measure Data Table shows change of height velocity at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1).
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IGF-1 | Difference in Height Velocity Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | 2.60 cm/year | Standard Deviation 1.64 |
| Standard Steroid Treatment Alone | Difference in Height Velocity Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | -0.06 cm/year | Standard Deviation 1.69 |
p-value: <0.000195% CI: [-3.78, -1.55]t-test, 2 sided
Secondary
Difference in North Star Ambulatory Assessment (NSAA) Score Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline
Outcome Measure Data Table shows change of North Star Ambulatory Assessment (NSAA) score at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1). The NSAA is a 17-item scale that grades performance of various functional skills on a scale from 0 (unable), 1 (complete independently but with modifications), and 2 (complete without compensation). The range of NSAA score is from 0 to 34. The higher score indicates better motor function.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IGF-1 | Difference in North Star Ambulatory Assessment (NSAA) Score Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | -0.94 score on a scale | Standard Deviation 2.41 |
| Standard Steroid Treatment Alone | Difference in North Star Ambulatory Assessment (NSAA) Score Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline | -0.4 score on a scale | Standard Deviation 3 |
p-value: 0.5395% CI: [-1.26, 2.38]t-test, 2 sided