Clinical trial NCT02006680: Markers of Pubertal Suppression During Therapy for Precocious Puberty
Official title: Markers of Adequate Pubertal Suppression During Supprelin LA Therapy for Central Precocious Puberty
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Central Precocious Puberty
Keywords: Central Precocious Puberty
Suppression
Alpha Subunit
Leuprolide Stimulation Test
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Endo Pharmaceuticals
name: Atlantic Center for Research
name: Goryeb Children's Hospital
First posted: 2013-12-10
Enrollment: 4
Sex: FEMALE
Minimum age (years): 3
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Females diagnosed with central precocious puberty or rapidly progressive puberty based upon age at start of puberty, physical examination, serum hormone levels and bone age X-Ray will be recruited. This will be a convenience sample of children scheduled to receive Supprelin LA insert placement. The subjects will be recruited from two pediatric endocrinology clinic systems.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity and specificity of free alpha subunit of pituitary glycoprotein to identify subjects with appropriate pubertal suppression.
timeFrame: Up to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Morristown
country: United States
facility: Atlantic Center for Research
state: New Jersey
Study officials:
affiliation: University of Minnesota
name: Bradley S Miller, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: