Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment

Study Overview
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Brief Summary
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Boys with constitutional delay of growth and puberty (CDGP) should be offered evidence-based effective and safe treatment option. This study compares the effects of low-dose testosterone and aromatase inhibitor letrozole on pubertal progression. The hypothesis is that, in boys CDGP showing earliest signs of puberty, peroral letrozole (2.5 mg/d for 6 mo) induces faster biochemical and clinical progression of puberty as compared to low-dose intramuscular testosterone Rx ( 1mg/kg/mo for 6 mo). In addition, 10 or more boys who select watchful waiting instead of medication will provide background data on the natural progression of CDGP, and their data will not be used in primary statistical comparisons.

Official Title
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Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment

Conditions
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Constitutional Delay of Growth and Puberty

Intervention / Treatment
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* Drug: Testosterone
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Constitutional delay of growth and puberty Age 14 years or more mean testicular volume 2.5 ml or more and less than 4 ml serum testosterone level less than 5 nM OR as above, but serum testosterone 1 nM or more with normal DHEAS level, even if the mean testicular volume is less than 2.5 ml OR as above, but tanner stage G2 and testosterone level less than 3 nM Exclusion Criteria: Chronic diseases Primary or secondary hypogonadism Chromosomal anomalies Chronic medication that potentially adversely affects bone mineralization (excluding inhaled corticosteroid treatment)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Testosterone<br> 1mg/kg every 4 weeks for 6 months | Drug: Testosterone<br>* 1mg/kg every 4 weeks for 6 months<br>* Other names: Sustanon 250;|
| Active Comparator: Letrozole<br>2.5mg daily for 6 months | Drug: Letrozole<br>* 2.5mg daily for 6 months. Safety criteria: if testosterone level is above 30nM at 3 months, the dosage is reduced to 2.5mg every other day<br>* Other names: Femar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| testicular volume | Testes will be measured with a ruler to the nearest millimeter and volume will be calculated at 0, 6, and 12 mo | one year | 
| clinical and biochemical measures of pubertal progression | Activity of the hypothalamic-pituitary-gonadal axis, evaluated by genital and pubic hair stage of puberty according to Tanner; growth velocity (cm/yr); basal and gonadotropin-releasing hormone (GnRH)-stimulated gonadotropin levels; urinary luteinizing hormone levels; testosterone; inhibin B; anti-mullerian hormone (AMH) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone health | Several endpoints related to bone health | one year | 
| Psychosocial well-being | Psycho-social well-being will assessed with questionnaires. | one year | 
| Puberty-related metabolical and clinical changes | Biochemical and metabolical changes will be compared btw testosterone and letrozole treatment groups. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Constitutional, Puberty, Delay, Letrozole, Testosterone