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 19, 2013
Last verified: May 2013

November 2, 2010
May 19, 2013
November 2010
October 2016   (final data collection date for primary outcome measure)
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.
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 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 . 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.
Complete list of historical versions of study NCT01248416 on ClinicalTrials.gov Archive Site
  • 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.
  • To characterize bone density and bone turnover markers as well as bone morphology in all 3 groups. [ Time Frame: 3 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.
  • 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 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.
  • To assess the degree of suppression of aromatase using letrozole vs anastrozole using highly sensitive LCMSMS assays. [ Time Frame: 3 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.
Not Provided
Not Provided
 
Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature
A Randomized Controlled Trial Of The Use Of Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Idiopathic Short Stature
  • 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)
  • Active Comparator: Aromatase Inhibitor
    Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years
    Intervention: Drug: Aromatase Inhibitor
  • Active Comparator: Growth Hormone
    Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years
    Intervention: Drug: Growth Hormone
  • 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
    Interventions:
    • Drug: Aromatase Inhibitor
    • Drug: Growth Hormone
    • Drug: Aromatase Inhibitor and Growth Hormone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
77
October 2017
October 2016   (final data collection date for primary outcome measure)

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).
Male
12 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Chile
 
NCT01248416
180984
Yes
Nelly Mauras, Nemours Children's Clinic
Nemours Children's Clinic
  • Thrasher Research Fund
  • Genentech
  • Novartis
  • AstraZeneca
  • Pfizer
Principal Investigator: Nelly Mauras, MD Nemours Children's Clinic - Jacksonville
Nemours Children's Clinic
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP