Effect of a GnRH Injection on Ghrelin Concentrations in Girls With Suspected Premature Puberty

Effect of a GnRH Injection on Ghrelin Concentrations in Girls With Suspected Precocious Puberty

The purposes of the study is to investigate whether circulating levels of ghrelin decreases after an iv injection of GnRH in girls with suspected central premature puberty and to investigate the effects of different post sampling handling on the preservation of acylated ghrelin.

Study Overview

• Status: Completed
• Conditions: Puberty, Precocious
• Intervention / Treatment: Drug: Gonadotropin releasing hormone (GnRH); Drug: Sodium Chloride

Detailed Description

Patients with clinically suspected central premature puberty undergo a GnRH stimulation test to have an appropriate diagnosis. 20 such girls will be recruited to this study and a modified GnRH stimulation test will be done. The modification includes prolonged blood sampling time (0, 30, 60, 90, 120, and 150 min after the GnRH injection instead of the usual 0, 30, 60, and 90 min). The girls will also be investigated twice. In randomised order they will be given either GnRH or placebo (isotone saline), on different days. One week to one month will separate the different investigation days.

The proteinase inhibitor 4-(2-aminoethyl) benzene-sulfonyl fluoride hydrochlorid (AEBSF) will be added to some of the blood tubes, and hydrochloric acid will be added to some of the plasma. All plasma samples will be frozen and all analyses will be done at the same time. Acylated ghrelin will be analyzed by Millipore's specific ELISA kit and deacylated ghrelin will be analyzed by Cayman's specific ELISA kit.

Anthropometric data as well as pubertal state will be collected. P-glucose, S-insulin, S-follicle stimulating hormone (FSH), S-luteinizing hormone (LH), and S-estradiol will also be analyzed.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Örebro, Sweden, 701 85
    • Department of Paediatrics, Örebro University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female gender.
• Clinical suspicion of central precocious puberty.
• A GnRH stimulation test is to be performed to make appropriate diagnosis.

Exclusion Criteria:

• Age < 1 year.
• Weight < 10 kg.
• Untreated hypo- or hyperthyroidism.
• Diabetes of any kind.
• BMI > 3 z-score.
• Growth hormone treatment.
• Syndrome or suspected syndrome.
• Tumour or congenital malformation of the hypothalamus or the pituitary gland. (Neuroradiology does not have to be performed only because of the study.)
• On going ulcus ventriculi or the patient has gone through surgery that removed part of the ventricle or changed it markedly in any other way.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gonadotropin releasing hormone (GnRH); A single intravenous injection of gonadotropin releasing hormone GnRH (Relefact LHRH 0,1 mg/mL). Dose: 100 micrograms per square meter body surface. Maximal dose: 100 micrograms.	Drug: Gonadotropin releasing hormone (GnRH); Gonadotropin releasing hormone GnRH (Relefact LHRH) iv injection, single dose, 100 micrograms/square meter body surface, maximum dose: 100 microgram.; Other Names: Relefact LHRH
Placebo Comparator: Sodium chloride; A single intravenous injection of sodium chlorid (9 mg/mL). Dose: the same volume as the volume given/to be given with GnRH, that is maximal dose = 1 mL = 9 mg sodium chlorid.	Drug: Sodium Chloride; Sodium chlorid 9 mg/mL will be given as a single iv injection with the same volume as the volume used for the active substance injection.; Other Names: Saline; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ghrelin concentration after GnRH injection and after saline injection	Paired comparison will be done between the acylated ghrelin concentration after GnRH injection and the acylated ghrelin concentration after saline injection. Paired comparison will also be done between deacylated ghrelin concentration after GnRH injection and deacylated ghrelin concentration after saline injection.	30-150 min after iv injections

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deacylated ghrelin concentrations in samples treated with the inhibitor AEBSF, in samples treated with both AEBSF and hydrochloric acid, and in samples not treated with either AEBSF or hydrochloric acid	Concentrations of deacylated ghrelin will be compared between different handling procedures.	At baseline
Deacylated ghrelin concentrations in samples treated with the inhibitor AEBSF, in samples treated with both AEBSF and hydrochloric acid, and in samples not treated with either AEBSF or hydrochloric acid	Deacylated ghrelin concentrations will be compared at 150 min after iv injections between different handling procedures.	150 min after iv injections
Acylated ghrelin concentrations in samples treated with and without hydrochloric acid	Acylated ghrelin concentrations will be compared between different handling procedures.	0-150 min after iv injections

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: Uppsala-Örebro Regional Research Council
• Investigators: Principal Investigator: Maria Lodefalk, MD, PhD, Department of Paediatrics, Faculty of Medicine and Health, Örebro University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: April 10, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): May 1, 2015

Study Record Updates

• Last Update Posted (Actual): April 1, 2019
• Last Update Submitted That Met QC Criteria: March 28, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: children; females; ghrelin; randomized, controlled study; GnRH
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: OLL-430981

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No