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

Phase 3
Completed
Conditions
Idiopathic Short Stature
Interventions
Drug: Aromatase Inhibitor
Drug: Aromatase Inhibitor and Growth Hormone
Registration Number
NCT01248416
Lead Sponsor
Nemours Children's Clinic
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
76
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Aromatase InhibitorAromatase InhibitorAnastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years
Aromatase Inhibitor and Growth HormoneAromatase InhibitorAnastrozole 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
Aromatase Inhibitor and Growth HormoneAromatase Inhibitor and Growth HormoneAnastrozole 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
Growth HormoneGrowth HormoneSomatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years
Aromatase Inhibitor and Growth HormoneGrowth HormoneAnastrozole 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
Primary Outcome Measures
NameTimeMethod
Change in Height0 to 24 months

Differences in height gains

Change in Predicted Height0 to 24 months

Primary efficacy end point: change in predicted height (cm) from baseline at 24 months based on change in bone age (years)

Secondary Outcome Measures
NameTimeMethod
Change in Testosterone0 to 24 months
Change in IGF-I Concentrations0 to 24 months
Change in Bone Density z Score Adjusted for Height0 to 24 months
Change in Lean Body Mass0 to 24 months
Change in Body Mass Index0 to 24 months
Change in Estradiol0 to 24 months

Those taking AI alone or AI/GH combined were grouped by type, either anastrozole or letrozole.

Change in Estrone0 to 24 months

Trial Locations

Locations (3)

Veronica Mericq, MD

🇨🇱

Santiago, Chile

Nemours Children's Clinic

🇺🇸

Orlando, Florida, United States

Nemours Children's Clinic- Jefferson

🇺🇸

Philadelphia, Pennsylvania, United States

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