Clinical Trial: Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:
Sponsor: Nemours Children's Clinic

Current Primary Outcome: 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 ]

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.


Original Primary Outcome: 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 ]

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.


Current Secondary Outcome:

  • To characterize bone density and bone turnover markers as well as bone morphology in all 3 groups. [ Time Frame: 3 to 4 years ]
    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 ]
    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 ]
    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.


Original Secondary Outcome:

  • To characterize bone density and bone turnover markers as well as bone morphology in all 3 groups. [ Time Frame: 3 years ]
    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 ]
    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 ]
    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.


Information By: Nemours Children's Clinic

Dates:
Date Received: November 2, 2010
Date Started: November 2010
Date Completion:
Last Updated: September 22, 2016
Last Verified: September 2016