NCT01248416

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
76

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2010

Longer than P75 for phase_3

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2010

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

November 2, 2010

Completed
23 days until next milestone

First Posted

Study publicly available on registry

November 25, 2010

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2016

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

June 7, 2018

Completed
Last Updated

August 7, 2018

Status Verified

July 1, 2018

Enrollment Period

5.8 years

First QC Date

November 2, 2010

Results QC Date

October 29, 2017

Last Update Submit

July 9, 2018

Conditions

Keywords

AromataseGrowthLetrozoleAnastrozoleGHChildrenPuberty

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (7)

  • 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

  • +2 more secondary outcomes

Study Arms (3)

Aromatase Inhibitor

ACTIVE COMPARATOR

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

Drug: Aromatase Inhibitor

Growth Hormone

ACTIVE COMPARATOR

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

Drug: Growth Hormone

Aromatase Inhibitor and Growth Hormone

ACTIVE COMPARATOR

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 InhibitorDrug: Growth HormoneDrug: Aromatase Inhibitor and Growth Hormone

Interventions

Also known as: Arimidex (Anastrozole), Femara (Letrozole)
Aromatase InhibitorAromatase Inhibitor and Growth Hormone
Also known as: Nutropin (Somatropin), Genotropin (Somatropin)
Aromatase Inhibitor and Growth HormoneGrowth Hormone
Also known as: Arimidex (Anastrozole), Femara (Letrozole), Nutropin (Somatropin), Genotropin (Somatropin)
Aromatase Inhibitor and Growth Hormone

Eligibility Criteria

Age12 Years - 18 Years
Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Clinic

Orlando, Florida, 32801, United States

Location

Nemours Children's Clinic- Jefferson

Philadelphia, Pennsylvania, 19107, United States

Location

Veronica Mericq, MD

Santiago, Chile

Location

Related Publications (1)

  • 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.

MeSH Terms

Interventions

Aromatase InhibitorsAnastrozoleLetrozoleGrowth HormoneHuman Growth Hormone

Intervention Hierarchy (Ancestors)

Steroid Synthesis InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesEstrogen AntagonistsHormone AntagonistsHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of DrugsNitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPituitary Hormones, AnteriorPituitary HormonesPeptide HormonesHormonesPeptidesAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
Dr. Nelly Mauras
Organization
Nemours Children's Clinic

Study Officials

  • Nelly Mauras, MD

    Nemours Children's Clinic Jacksonville

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief, Division of Endocrinology, Diabetes & Metabolism

Study Record Dates

First Submitted

November 2, 2010

First Posted

November 25, 2010

Study Start

November 1, 2010

Primary Completion

September 1, 2016

Study Completion

September 1, 2016

Last Updated

August 7, 2018

Results First Posted

June 7, 2018

Record last verified: 2018-07

Locations