Skeletal Muscle Effects of GH in Boys

Study Overview
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Brief Summary
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The purpose of the study is to measure the functional effects of recombinant GH in skeletal muscle, in addition to growth promotion, in short prepubertal boys with either growth hormone deficiency or idiopathic short stature. Patients will be similarly short. The investigators will also compare these values in the short stature cohort to those obtained in testing performed in normally growing age-matched healthy control boys not on GH. The group on GH will be studied before and after 6 and 12 months of GH treatment.

Detailed Description
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Prepubertal boys with significant short stature (height SDS ≤-2.0) diagnosed with either GH deficiency or idiopathic short stature (ISS) who are identified as candidates for GH treatment will recruited. Subjects will have a battery of studies to assess skeletal muscle strength, agility, power and endurance, as well as assessment of body composition and energy expenditure before and after GH administration. GH (Somatropin) treatment at standard doses will be given as daily injections at bedtime. Subjects will be followed at three-month intervals per the clinical routine, when anthropometric measurements will be obtained. Baseline studies will be repeated at 6 and 12 months from initiation of treatment, each patient will serve as his own control pre and post GH. A group of normally statured healthy boys will have the same testing as the study patients but without GH treatment to assess the impact of natural growth on the muscle measures above.

Official Title
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Recombinant Human Growth Hormone (GH): Effects on Metabolic Profile, Body Composition and Skeletal Muscle Strength and Function in Pre-pubertal Short Boys With and Without GH Deficiency

Conditions
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Growth Hormone Deficiency, Idiopathic Short Stature

Intervention / Treatment
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* Drug: Somatropin injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Short Stature Group 30 boys between 6-11 years of age Prepubertal Short stature (height ≤ -2SDS) due to either GH deficiency or idiopathic Stable treatment of other pituitary hormone deficiencies Naïve to GH therapy, or GH discontinued at least 6 months prior to study Normal Stature Group 15 boys between 6-11 years of age Prepubertal Normal height (10th to 90th%) Exclusion Criteria: Actively growing brain tumors Chronic medical conditions that could affect study outcomes Long-term steroid use Intense regular physical training programs or organized team sports

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Short Stature Boys<br>Prepubertal boys with short stature defined as a height ≤-2 SDS with either GH deficiency (defined as peak GH responses to pharmacologic stimuli <10ng/ml) or idiopathic short stature (i.e., no identifiable pathology) will be studied pre and post 12 months of GH therapy. | Drug: Somatropin injection<br>* Boys with short stature will be studied for measures of: skeletal muscle strength, power, and endurance muscle agility lean body mass accrual bone mineral density and resting energy expenditure before and after 6 months and 12 months of GH administration<br>* Other names: Norditropin;|
| Normally Statured Boys<br>A group of 15 healthy, normally statured (between 10th- 90th %), age-matched boys not on Growth Hormone replacement, preferably siblings (although not exclusively), will be recruited to serve as healthy controls. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle strength (Newtons) | Upper and lower body muscle strength will be assessed using a handheld dynamometer for manual muscle testing of peak force | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle power (Watts) | Lower extremity power will be assessed by vertical jump performed using a Power time mat | 12 months | 
| Muscle agility (seconds) | Muscle agility will be assessed by a timed shuttle run | 12 months | 
| Muscle endurance | Upper body muscular endurance will be assessed using a modified push up test for repetitions | 12 months | 
| Lean body mass accrual | Assessed by dual energy x-ray absorptiometry (DEXA) scan of the whole body | 12 months | 
| Bone mineral density | Assessed by DEXA scan of the lumbar spine and whole body | 12 months | 
| Resting energy expenditure | Indirect calorimetry will be performed after overnight fast | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GH, muscle strength, prepubertal, boys, short stature, GH treatment, muscle agility