Short Stature
Conditions
Brief summary
The purpose of the study is to determine if there are differences in the final height or hormone profile of short pubertal boys placed on different forms of aromatase inhibitor now routinely used to increase stature: Anastrozole and Letrozole. It also should determine if there are differences in the side effect profiles of the two drugs to be used.
Interventions
DRUGLetrozole
DRUGAnastrozole
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Current height less than 5th percentile AND/OR * Predicted adult height (based on bone age) more than 10 cm below target height (mid parental height) * Evidence of puberty: physical signs and serum luteinizing hormone \> 0.3 IU/L and testosterone \> 15 ng/dl
Exclusion criteria
* Bone age reading more than 14.0 years * Follicle stimulating hormone \> 20 IU/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Predicted Adult Height at Year 3 | Year 3 | Heights will be obtained by physical exam every 6 months during treatment. Skeletal maturation will be assessed from an x-ray by the method of Greulich and Pyle at baseline and every 12 months until the end of treatment. Predicted adult height will be calculated at baseline and at the end of treatment based upon measured height and skeletal maturation (bone age). |
Secondary
| Measure | Time frame |
|---|---|
| Serum Testosterone | Baseline, year 3 |
| Dihydrotestosterone | Baseline, year 3 |
| Androstenedione | Baseline, year 3 |
| Luteinizing Hormone | Baseline, year 3 |
| Inhibin B | Baseline, year 3 |
| Insulin-like Growth Factor Type 1 | Baseline, year 3 |
| Estradiol | Baseline, year 3 |
| Estrone | Baseline, year 3 |
| Number of Adverse Events Related to Acne or Bone Fracture | 3 years |
| Follicle Stimulating Hormone | Baseline, year 3 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Letrozole Participants receive letrozole 2.5 mg daily | 30 |
| Anastrozole Participants receive anastrozole 1 mg daily | 35 |
| Total | 65 |
Baseline characteristics
| Characteristic | Anastrozole | Total | Letrozole |
|---|---|---|---|
| Age, Continuous | 13.9 years STANDARD_DEVIATION 1.5 | 13.9 years STANDARD_DEVIATION 1.4 | 13.9 years STANDARD_DEVIATION 1.2 |
| Bone age | 156.3 months STANDARD_DEVIATION 12.2 | 156.2 months STANDARD_DEVIATION 9.9 | 156.1 months STANDARD_DEVIATION 6.6 |
| Predicted Adult Height | 167.3 cm STANDARD_DEVIATION 6.9 | 167.2 cm STANDARD_DEVIATION 6.4 | 167.2 cm STANDARD_DEVIATION 5.8 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 35 participants | 65 participants | 30 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 65 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 40 |
| other Total, other adverse events | 12 / 39 | 10 / 40 |
| serious Total, serious adverse events | 0 / 39 | 2 / 40 |
Outcome results
Primary
Predicted Adult Height at Year 3
Heights will be obtained by physical exam every 6 months during treatment. Skeletal maturation will be assessed from an x-ray by the method of Greulich and Pyle at baseline and every 12 months until the end of treatment. Predicted adult height will be calculated at baseline and at the end of treatment based upon measured height and skeletal maturation (bone age).
Time frame: Year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Letrozole | Predicted Adult Height at Year 3 | 167.8 cm | Standard Deviation 5.8 |
| Anastrozole | Predicted Adult Height at Year 3 | 169.4 cm | Standard Deviation 5.1 |
Secondary
Androstenedione
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Androstenedione | Baseline | 35.3 ng/dL | Standard Deviation 13.1 |
| Letrozole | Androstenedione | Year 3 | 79.9 ng/dL | Standard Deviation 21.5 |
| Anastrozole | Androstenedione | Baseline | 37.4 ng/dL | Standard Deviation 21.4 |
| Anastrozole | Androstenedione | Year 3 | 77.9 ng/dL | Standard Deviation 28.2 |
Secondary
Dihydrotestosterone
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Dihydrotestosterone | Baseline | 22.5 ng/dL | Standard Deviation 11.3 |
| Letrozole | Dihydrotestosterone | Year 3 | 65.0 ng/dL | Standard Deviation 20.2 |
| Anastrozole | Dihydrotestosterone | Baseline | 19.1 ng/dL | Standard Deviation 9.7 |
| Anastrozole | Dihydrotestosterone | Year 3 | 44.1 ng/dL | Standard Deviation 23.5 |
Secondary
Estradiol
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Estradiol | Baseline | 4.9 pg/mL | Standard Deviation 3.6 |
| Letrozole | Estradiol | Year 3 | 2.7 pg/mL | Standard Deviation 2.1 |
| Anastrozole | Estradiol | Baseline | 4.7 pg/mL | Standard Deviation 4.7 |
| Anastrozole | Estradiol | Year 3 | 6.2 pg/mL | Standard Deviation 2.5 |
Secondary
Estrone
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Estrone | Baseline | 8.7 pg/mL | Standard Deviation 4.8 |
| Letrozole | Estrone | Year 3 | 2.7 pg/mL | Standard Deviation 0.3 |
| Anastrozole | Estrone | Baseline | 8.0 pg/mL | Standard Deviation 4.9 |
| Anastrozole | Estrone | Year 3 | 3.5 pg/mL | Standard Deviation 3.2 |
Secondary
Follicle Stimulating Hormone
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Follicle Stimulating Hormone | Year 3 | 6.6 mIU/mL | Standard Deviation 2.4 |
| Letrozole | Follicle Stimulating Hormone | Baseline | 3.3 mIU/mL | Standard Deviation 1.9 |
| Anastrozole | Follicle Stimulating Hormone | Year 3 | 4.5 mIU/mL | Standard Deviation 2.9 |
| Anastrozole | Follicle Stimulating Hormone | Baseline | 2.5 mIU/mL | Standard Deviation 1.3 |
Secondary
Inhibin B
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Inhibin B | Baseline | 203.4 pg/mL | Standard Deviation 55 |
| Letrozole | Inhibin B | Year 3 | 257.6 pg/mL | Standard Deviation 61.1 |
| Anastrozole | Inhibin B | Baseline | 217.0 pg/mL | Standard Deviation 65.2 |
| Anastrozole | Inhibin B | Year 3 | 262.1 pg/mL | Standard Deviation 97.9 |
Secondary
Insulin-like Growth Factor Type 1
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Insulin-like Growth Factor Type 1 | Baseline | 306.2 ng/mL | Standard Deviation 112.8 |
| Letrozole | Insulin-like Growth Factor Type 1 | Year 3 | 226.1 ng/mL | Standard Deviation 54.4 |
| Anastrozole | Insulin-like Growth Factor Type 1 | Baseline | 306.9 ng/mL | Standard Deviation 112.9 |
| Anastrozole | Insulin-like Growth Factor Type 1 | Year 3 | 298.7 ng/mL | Standard Deviation 78.8 |
Secondary
Luteinizing Hormone
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Luteinizing Hormone | Baseline | 2.3 mIU/mL | Standard Deviation 1.5 |
| Letrozole | Luteinizing Hormone | Year 3 | 4.7 mIU/mL | Standard Deviation 1.9 |
| Anastrozole | Luteinizing Hormone | Baseline | 1.8 mIU/mL | Standard Deviation 1.1 |
| Anastrozole | Luteinizing Hormone | Year 3 | 3.4 mIU/mL | Standard Deviation 2 |
Secondary
Number of Adverse Events Related to Acne or Bone Fracture
Time frame: 3 years
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Letrozole | Number of Adverse Events Related to Acne or Bone Fracture | Acne | 3 events |
| Letrozole | Number of Adverse Events Related to Acne or Bone Fracture | Fracture | 3 events |
| Anastrozole | Number of Adverse Events Related to Acne or Bone Fracture | Fracture | 5 events |
| Anastrozole | Number of Adverse Events Related to Acne or Bone Fracture | Acne | 3 events |
Secondary
Serum Testosterone
Time frame: Baseline, year 3
Population: Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Letrozole | Serum Testosterone | Baseline | 213.1 ng/dL | Standard Deviation 133.7 |
| Letrozole | Serum Testosterone | Year 3 | 882.3 ng/dL | Standard Deviation 250.5 |
| Anastrozole | Serum Testosterone | Baseline | 162.1 ng/dL | Standard Deviation 124.6 |
| Anastrozole | Serum Testosterone | Year 3 | 680.1 ng/dL | Standard Deviation 179.5 |