Markers of Pubertal Suppression During Therapy for Precocious Puberty

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

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®.

Study Overview

• Status: Terminated
• Conditions: Central Precocious Puberty

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.

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Center for Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 9 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Children with Central Precocious Puberty; 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?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Endo Pharmaceuticals; Atlantic Center for Research; Goryeb Children's Hospital
• Investigators: Principal Investigator: Bradley S Miller, MD, PhD, University of Minnesota

Publications and helpful links

Helpful Links

• Pedatric Diabetes and Endocrinology at Goryeb Children's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2013
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: December 4, 2013
• First Submitted That Met QC Criteria: December 4, 2013
• First Posted (ESTIMATE): December 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Suppression; Central Precocious Puberty; Alpha Subunit; Leuprolide Stimulation Test
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious
• Other Study ID Numbers: 1303M29681