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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Thrasher Research Fund
Genentech
Novartis
AstraZeneca
Pfizer
Information provided by (Responsible Party):
Nelly Mauras, Nemours Children's Clinic
ClinicalTrials.gov Identifier:
NCT01248416
First received: November 2, 2010
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Idiopathic Short Stature
Drug: Aromatase Inhibitor
Drug: Growth Hormone
Drug: Aromatase Inhibitor and Growth Hormone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Nemours Children's Clinic:

Primary Outcome Measures:
  • To assess the safety and efficacy of AIs alone, vs. GH alone, vs. AIs and GH increasing adult height potential in adolescent boys with idiopathic short stature treated for 2 years. [ Time Frame: 3 to 4 years ] [ Designated as safety issue: Yes ]
    Adolescent boys with idiopathic short stature will be randomized to either AI orally (anastrozole or letrozole), GH subcutaneously or AI with GH combination for 2 years and 1 extra year post treatment follow up . Subjects who have completed 2 years of therapy, may receive 1 additional year of therapy if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy. Blood samples and bone age X rays will be obtained during routine clinic visits. Primary efficacy end point: change in predicted height (cm) from baseline at 24 months based on change in bone age (years). Differences in height gains (cm) will be compared among the 3 groups as well. Number of participants with adverse events as a measure of safety and tolerability will be recorded.


Secondary Outcome Measures:
  • To characterize bone density and bone turnover markers as well as bone morphology in all 3 groups. [ Time Frame: 3 to 4 years ] [ Designated as safety issue: Yes ]
    This secondary end point includes the changes in bone density (gm/cm2), IGF-I concentrations, and bone markers concentrations. A Dexa scan with a lateral view of the thoracic spine as well as blood work will be routinely done at baseline, 1 year and 2 years and changes in the 3 groups compared over time. Subjects who have completed 2 years of therapy, may receive a 3 year scan if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy.

  • To investigate if the combination of GH with an AI has additive effects increasing lean body mass in puberty as compared to each compound alone. [ Time Frame: 3 to 4 years ] [ Designated as safety issue: Yes ]
    This secondary outcome measures lean body mass (kg) by Dexa scan and body mass index measurements at baseline, 1 and 2 years. A comparison of the changes among the 3 groups over time will be done. Subjects who have completed 2 years of therapy, may receive 1 additional year of therapy if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy.

  • To assess the degree of suppression of aromatase using letrozole vs anastrozole using highly sensitive LCMSMS assays. [ Time Frame: 3 to 4 years ] [ Designated as safety issue: No ]
    Data on the subjects using either AI will be used for the overall efficacy analysis. The degree of suppression of estradiol by each AI will be indirectly assessed by using a sensitive estradiol assay. This secondary outcome measures serum testosterone, estrone and plasma estradiol concentrations. Subjects who have completed 2 years of therapy, may receive 1 additional year of therapy if at 24 months they have: a) Sustained growth velocity of ≥ 3cm/yr, and b) Bone age ≤14 1/2 years, and c) Subject and family wish to continue therapy.


Enrollment: 77
Study Start Date: November 2010
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aromatase Inhibitor
Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years
Drug: Aromatase Inhibitor
Other Names:
  • Arimidex (Anastrozole)
  • Femara (Letrozole)
Active Comparator: Growth Hormone
Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years
Drug: Growth Hormone
Other Names:
  • Nutropin (Somatropin)
  • Genotropin (Somatropin)
Active Comparator: Aromatase Inhibitor and Growth Hormone
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
Other Names:
  • Arimidex (Anastrozole)
  • Femara (Letrozole)
Drug: Growth Hormone
Other Names:
  • Nutropin (Somatropin)
  • Genotropin (Somatropin)
Drug: Aromatase Inhibitor and Growth Hormone
Other Names:
  • Arimidex (Anastrozole)
  • Femara (Letrozole)
  • Nutropin (Somatropin)
  • Genotropin (Somatropin)

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01248416

Locations
United States, Florida
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Nemours Children's Clinic
Orlando, Florida, United States, 32801
United States, Pennsylvania
Nemours Children's Clinic- Jefferson
Philadelphia, Pennsylvania, United States, 19107
Chile
Veronica Mericq, MD
Santiago, Chile
Sponsors and Collaborators
Nemours Children's Clinic
Thrasher Research Fund
Genentech
Novartis
AstraZeneca
Pfizer
Investigators
Principal Investigator: Nelly Mauras, MD Nemours Children's Clinic Jacksonville
  More Information

No publications provided

Responsible Party: Nelly Mauras, Chief, Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic
ClinicalTrials.gov Identifier: NCT01248416     History of Changes
Other Study ID Numbers: 180984
Study First Received: November 2, 2010
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Nemours Children's Clinic:
Aromatase
Growth
Letrozole
Anastrozole
GH
Children
Puberty

Additional relevant MeSH terms:
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Endocrine System Diseases
Hormones
Letrozole
Anastrozole
Aromatase Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on August 28, 2014