Markers of Pubertal Suppression During Therapy for Precocious Puberty

Study Overview
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Brief Summary
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The best way to measure whether treatment of children with central precocious puberty is working is to do a hormone stimulation test (leuprolide stimulation test) that requires injection of a medication and multiple blood draws to see if the hormonal response is suppressed (blocked). The hypothesis of this study is that random measurement of the free alpha subunit of pituitary glycoprotein, a protein related to the pituitary hormones that stimulate puberty, will provide an adequate alternative to the leuprolide stimulation testfor monitoring efficacy of pubertal suppression with Supprelin LA®.

Detailed Description
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During clinical trials of Supprelin LA®, leuprolide stimulation tests were performed to determine adequacy of suppression. However, the use of this stimulation test to monitor suppression requires an expensive medication and collection of multiple blood samples. Alternative methods of monitoring pubertal suppression during gonadotropin releasing hormone receptor agonist (GnRHa) therapy have included both random and trough levels of Luteinizing Hormone (LH), estradiol or inhibin B. Recently, the free alpha subunit of pituitary glycoprotein (FASPG) has also been shown to be a potentially useful marker of hormonal suppression (Hirsch HJ, et al, JCEM 95:2841, 2010) as it undergoes a paradoxical rise following initiation of therapy, and reverts to baseline upon completion. In this investigator-initiated pilot study we will evaluate novel markers of pubertal suppression in children receiving standard of care gonadotropin releasing hormone receptor agonist therapy for the treatment of central precocious puberty. Children with central precocious puberty who have selected treatment with Supprelin LA will undergo hormonal testing of markers of pubertal activity before and after placement of the Supprelin LA insert.

Official Title
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Markers of Adequate Pubertal Suppression During Supprelin LA Therapy for Central Precocious Puberty

Conditions
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Central Precocious Puberty

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Age: 3 to 9 years old, inclusive Diagnosis of Central Precocious or Rapidly Progressive Puberty Bone Age more than 1 year advanced (obtained within 6 months of screening) AND Breasts Tanner II or greater AND One of the following: Random LH > 1 mIU/mL Leuprolide-stimulated LH > 4 mIU/mL Random estradiol > 20 pg/mL Leuprolide-stimulated 24 hour estradiol >20 pg/mL Naïve to GnRHa therapy Approved to receive Supprelin LA® therapy Have an acceptable surrogate capable of giving consent on the subject's behalf. Exclusion Criteria: Previous GnRHa therapy Presence of peripheral precocious puberty including CAH

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 9 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children with Central Precocious Puberty<br>Children with Central Precocious Puberty will have hormonal testing of markers of puberty up to 30 days prior to placement of a Supprelin LA insert and 28-97 days after placement of the Supprelin LA insert. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of free alpha subunit of pituitary glycoprotein to identify subjects with appropriate pubertal suppression. | The primary outcome of the study will be the sensitivity and specificity of a subject having elevated random FASPG values (> 0.6 ng/mL) to identify subjects who are appropriately suppressed based upon a leuprolide-stimulated LH <4 mIU/mL. This outcome will be based upon results of puberty hormone suppression testing obtained 28-97 days after placement of the Supprelin LA insert. | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Precocious Puberty, Suppression, Alpha Subunit, Leuprolide Stimulation Test