Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature

Study Overview
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Brief Summary
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When treating very short children in puberty we are time-limited, as sex hormones cause the growth plates to fuse and growth to end. Growth Hormone (GH), plus drugs that stop puberty, increase height potential, but leave children sexually infantile at a critical time in development. Human and animal data show that estrogen, in females and males, is a principal regulator of the fusion of the growth plate in puberty. Using aromatase inhibitors (AIs), which block testosterone to estrogen conversion, in boys with different growth disorders, we have shown that AIs may have beneficial effects enhancing height potential in growth-retarded males, without affecting their puberty. However, no direct comparison of the effect of AIs alone vs. conventional GH treatment has been done to date. This study will assess the effect of AIs alone, GH alone and combination treatment in enhancing height potential in adolescent boys with idiopathic short stature.

Official Title
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A Randomized Controlled Trial Of The Use Of Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature

Conditions
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Idiopathic Short Stature

Intervention / Treatment
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* Drug: Aromatase Inhibitor
* Drug: Growth Hormone
* Drug: Aromatase Inhibitor and Growth Hormone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males: Ages: 12 - less than 18 years. Bone age less than 14 ½ years at study initiation. Presence of puberty. Idiopathic short stature will be defined as a short child equal or less than -2SD for height, with normal GH responses to stimuli (> or = 5ng/ml to at least 2 secretagogues) or a normal IGF-I and BP-3, normal body proportions and no other identifiable growth pathology. Accurate growth data for at least 6 months at baseline is available. Exclusion Criteria: Chronic illnesses. Chronic use of glucocorticosteroids. Previous use of hormonal treatment with AIs, sex steroids or GH in the preceding 6 months. Birth weight small for gestational age (SGA).

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Male

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aromatase Inhibitor<br>Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years | Drug: Aromatase Inhibitor<br> <br> * Other names: Femara (Letrozole);|
| Active Comparator: Growth Hormone<br>Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years | Drug: Growth Hormone<br> <br> * Other names: Genotropin (Somatropin);|
| Active Comparator: Aromatase Inhibitor and Growth Hormone<br>Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years | Drug: Aromatase Inhibitor<br> <br> * Other names: Femara (Letrozole);Drug: Growth Hormone<br> <br> * Other names: Genotropin (Somatropin);Drug: Aromatase Inhibitor and Growth Hormone<br> <br> * Other names: Genotropin (Somatropin);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Height | Differences in height gains | 0 to 24 months | 
| Change in Predicted Height | Primary efficacy end point: change in predicted height (cm) from baseline at 24 months based on change in bone age (years) | 0 to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Density z Score Adjusted for Height |  | 0 to 24 months | 
| Change in Lean Body Mass |  | 0 to 24 months | 
| Change in Body Mass Index |  | 0 to 24 months | 
| Change in IGF-I Concentrations |  | 0 to 24 months | 
| Change in Testosterone |  | 0 to 24 months | 
| Change in Estradiol | Those taking AI alone or AI/GH combined were grouped by type, either anastrozole or letrozole. | 0 to 24 months | 
| Change in Estrone |  | 0 to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aromatase, Growth, Letrozole, Anastrozole, GH, Children, Puberty