Efficacy Safety of Granulocyte Colony-stimulating Factor Treatment Children and Adolescents With Muscular Dystrophy

Study Overview
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Brief Summary
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Importance: Currently the gold standard treatment for ambulant patients is corticosteroids. Granulocyte colony-stimulating factor (G-CSF) has been reported to exert the proliferation of satellite cells, the regulation of myoblast proliferation, and the differentiation and promotion of muscle regeneration and repair. Objectives To evaluate the safety and efficacy of G-CSF in children and adolescents with muscular dystrophies Duchenne muscular dystrophy, Becker muscular dystrophy , Fascioscapulohumeral dystrophy. Design, Setting, and Participants: Patients aged 5-15 with diagnosed muscular dystrophies will be included in an open study. Patients wheelchair-bound and and mobile and self-independent can participate in the study. Patients also treated with steroids can participate in this study. Clinical examination and physiotherapeutic and laboratory tests will be perform. G-CSF (5mcg/kg/body/d) is given subcutaneously for five consecutive days during the 1st, 2nd, 3rd. 6th and 12th months. Manual muscle testing (Lovett test) of the upper and lower extremities, isometric force with the hand dynamometer, and the 6MWT (six minute walk test) are measured before and after therapy.

Detailed Description
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Importance: Currently the gold standard treatment for ambulant patients is corticosteroids. Granulocyte colony-stimulating factor (G-CSF) has been reported to exert the proliferation of satellite cells, the regulation of myoblast proliferation, and the differentiation and promotion of muscle regeneration and repair. Objectives To evaluate the safety and efficacy of G-CSF in children and adolescents with muscular dystrophies Duchenne muscular dystrophy, Becker muscular dystrophy , Fascioscapulohumeral dystrophy. Design, Setting, and Participants: Patients aged 5-15 with diagnosed muscular dystrophies will be included in an open study. Patients wheelchair-bound and and mobile and self-independent can participate in the study. Patients also treated with steroids can participate in this study. Clinical examination and physiotherapeutic and laboratory tests will be perform. G-CSF (5mcg/kg/body/d) is given subcutaneously for five consecutive days during the 1st, 2nd, 3rd. 6th and 12th months. Blood is sampled before G-CSF administration and on the 5th day of each treatment cycle. During each cycle of G-CSF administration physical therapy is also applied. Abdominal ultrasonography with a spleen assessment is performed before and after 7 days of G-CSF administration. Spirometry and electrocardiographic record are also performed. Side effects of G-CSF treatment will be assessed. Manual muscle testing (Lovett test) of the upper and lower extremities, isometric force with the hand dynamometer, and the 6MWT (six minute walk test) are measured before and after therapy. MRI of the gastrocnemius muscles will performed at the beginning and at the end of therapy.

Official Title
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Efficacy and the Safety of Granulocyte Colony-stimulating Factor Treatment in Children and Adolescents With Muscular Dystrophy: An Open Study

Conditions
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Increase Muscle Strength in Patients With Muscular Dystrophy

Intervention / Treatment
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* Drug: Granulocyte colony-stimulating factor (Filgrastim)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Muscular dystrophy - Duchenne muscular dystrophy, Becker muscular dystrophy, Fascioscapulohumeral dystrophy age 5-15 Exclusion Criteria: non- muscular dystrophy age below 5 years age over 15 years

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Granulocyte colony-stimulating factor<br>Granulocyte colony-stimulating factor Muscle strength Muscular dystrophy | Drug: Granulocyte colony-stimulating factor (Filgrastim)<br>* Drug administration<br>* Other names: Filgrastim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety based on number of participants with adverse events. | Adverse events will be monitored and scored for severity and related to the Granulocyte Colony-Stimulating Factor administration. | Seven years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle strength in patients with muscular dystrophy | The assessment of muscle strength of the upper and lower limbs by Lovett test. The evaluation isometric force of upper limbs with the hand dynamometer. Distance measurement in a 6-minute walk test (6MWT) by feet or wheelchair,6MWT before and after therapy. | Seven years | 
| Laboratory investigations in patients with muscular dystrophy | Blood count: Red blood cells 10^6/µL; Hemoglobin g/dl, Leucocytes 10^3/µL, Platelets 10^3/µL; biochemistry CRP - C Reactive Protein - mg/L; creatinine - mg/dL; glucose mg/dL, electrolytes, AST- U/L; ALT - U/L; cholesterol mg/dL; fibrinogen - mg/dL, partial thromboplastin time - sec; prothrombin time - sec, creatine kinase - U/L | Seven years | 
| Abdominal ultrasonography in patients with muscular dystrophy | Abdominal ultrasonography with a spleen measurement will be done before and after G-CSF administration | Seven years | 
| Electrocardiographic records in patients with muscular dystrophy | Electrocardiographic records wiil ibe done in patients with muscular Dystrophy before and after G-CSF administration. | Seven years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Granulocyte colony-stimulating factor, muscular dystrophy, muscle strength, children, adolescents