Clinical trial NCT01248416: Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature
Official title: A Randomized Controlled Trial Of The Use Of Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Short Stature
Keywords: Aromatase
Growth
Letrozole
Anastrozole
GH
Children
Puberty
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
name: Genentech, Inc.
name: Novartis
name: AstraZeneca
name: Pfizer
First posted: 2010-11-25
Enrollment: 76
Sex: MALE
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change in Height
timeFrame: 0 to 24 months
measure: Change in Predicted Height
timeFrame: 0 to 24 months
Secondary outcomes:
measure: Change in Bone Density z Score Adjusted for Height
timeFrame: 0 to 24 months
measure: Change in Lean Body Mass
timeFrame: 0 to 24 months
measure: Change in Body Mass Index
timeFrame: 0 to 24 months
measure: Change in IGF-I Concentrations
timeFrame: 0 to 24 months
measure: Change in Testosterone
timeFrame: 0 to 24 months
measure: Change in Estradiol
timeFrame: 0 to 24 months
measure: Change in Estrone
timeFrame: 0 to 24 months
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Philadelphia
country: United States
facility: Nemours Children's Clinic- Jefferson
state: Pennsylvania
city: Santiago
country: Chile
facility: Veronica Mericq, MD
Study officials:
affiliation: Nemours Children's Clinic Jacksonville
name: Nelly Mauras, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mauras N, Ross JL, Gagliardi P, Yu YM, Hossain J, Permuy J, Damaso L, Merinbaum D, Singh RJ, Gaete X, Mericq V. Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature. J Clin Endocrinol Metab. 2016 Dec;101(12):4984-4993. doi: 10.1210/jc.2016-2891. Epub 2016 Oct 6.