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

Nemours Children's Health

Status and phase: Completed; Phase 3

Conditions: Idiopathic Short Stature

Treatments: Drug: Growth Hormone; Drug: Aromatase Inhibitor; Drug: Aromatase Inhibitor and Growth Hormone

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01248416

180984

Details and patient eligibility

About

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.

Enrollment: 76 patients

Sex: Male

Ages: 12 to 18 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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76 participants in 3 patient groups

Aromatase Inhibitor

Active Comparator group

Description:

Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years

Treatment:

Drug: Aromatase Inhibitor

Growth Hormone

Active Comparator group

Description:

Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years

Treatment:

Drug: Growth Hormone

Aromatase Inhibitor and Growth Hormone

Active Comparator group

Description:

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

Treatment:

Drug: Aromatase Inhibitor and Growth Hormone

Drug: Aromatase Inhibitor

Drug: Growth Hormone