Follicle-Stimulating Hormone (FSH) and the Onset of Puberty

NCT ID: NCT00734279

Last Updated: 2017-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2010-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to determine if the timing of the onset of puberty may be affected by FSH-regulatory peptides.

We will determine how these peptides relate to FSH production in prepubertal and pubertal children by comparing the regulation of FSH control in children with precocious (early) puberty and delayed puberty.

In this pilot study, we will stimulate the pubertal axis using an agonist of GnRH to determine the pubertal response of activin-A, inhibin-A and -B and follistatin.

To determine baseline FSH secretion and FSH-regulatory peptide tone, we will block GnRH with a specific antagonist.

These studies should lead to a better understanding of the role of FSH in controlling the onset of puberty and the pathogenesis of pubertal disorders.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Girls begin puberty earlier and have as much as a 5-fold increase in incidence of precocious puberty as do boys, while boys are more likely to have delayed adolescence compared to girls.

The reasons for sex differences in the timing of puberty and sex-based variation in expression of pubertal disorders are not known.

Puberty is heralded by an increase in the episodic release of luteinizing hormone (LH) under the control of increased gonadotropin-releasing hormone (GnRH) release. It has been thought that sex differences in central nervous system restraint of GnRH and subsequently of LH secretion account for the differences in timing of onset of puberty in boys and girls.

Follicle-stimulating hormone (FSH) secretion is readily detected prior to the onset of puberty and exhibits sexual dimorphism in basal and GnRH-stimulated concentrations. Thus, assessment of factors regulating FSH secretion during childhood may enhance our understanding of sex differences in pubertal development and the pathogenesis of precocious puberty.

Although FSH is secreted under the control of GnRH, FSH is also secreted constitutively under the control of a group of peptides collectively known as the FSH-regulatory proteins. These peptides include activins, peptides that increase FSH secretion and inhibins and follistatins, peptides that suppress FSH secretion.

Gonadal inhibins inhibit FSH via endocrine negative feedback, but their production during puberty is only beginning to be understood. Activin and follistatin have been thought to have a principle paracrine role in FSH regulation but recent data have demonstrated these peptides have an endocrine role as well.

We hypothesize that differences in elaboration of activins, inhibins, and follistatin that alter FSH constitutive secretion underlie precocious and delayed puberty in boys and girls and account, in part, for sex differences in pubertal timing.

Specifically we expect that the inhibitory regulators, inhibins and/or follistatins, will be lower while the stimulatory regulator, activin, will be higher in early compared to delayed puberty.

FSH and the Onset of Puberty is a case control study comparing boys with precocious puberty to boys with delayed adolescence and girls with precocious puberty to girls with delayed adolescence.

Hypothesis: Basal and GnRH agonist-stimulated activin concentrations will be greater and inhibin concentrations lower in children with early puberty than in children with delayed adolescence, and the GnRH antagonist, ganirelix, will decrease activin concentrations in children with early puberty but not in delayed adolescence.

Specific Aim 1: Determine the degree to which FSH-regulatory peptides, compared to gonadotropin-releasing hormone (GnRH), control FSH secretion in children by suppressing GnRH with ganirelix in children with early and delayed adolescence.

Specific Aim 2: Determine the role of FSH-regulatory peptides in control of timing of onset of puberty by comparing their concentrations with and without GnRH stimulation of FSH in children with precocious puberty and delayed adolescence.

Specific Aim 3: Determine the role of GnRH in control of the FSH-regulatory peptides by comparing activin, inhibin and follistatin concentrations in children with delayed adolescence due to constitutional growth delay to those with delayed adolescence from hypogonadotropic hypogonadism

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Delayed Puberty Precocious Puberty

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Puberty Delayed Early Precocious Peripubertal Gonadotropin FSH LH

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

Girls with Early Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion

Group Type EXPERIMENTAL

Leuprolide Acetate - Early Puberty Leuprolide Visit

Intervention Type DRUG

Dose of 10 mcg/kg Sub cutaneous once at 0800 on day 2 of the Early Puberty Luprolide Visit

Ganirelix - Early Puberty Ganirelix Visit

Intervention Type DRUG

Dose of 2.5 mcg/kg Sub-cutaneous once at 17:30 on day 1 of the Early Puberty Ganirelix Visit and once at 08:00 on day 2 of the Early Puberty Ganirelix Visit

2

Girls with Delayed Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion

Group Type EXPERIMENTAL

Ganirelix - Delayed Puberty Ganirelix Visit

Intervention Type DRUG

Ganirelix is administered at a dose of 2.5 mcg/kg sub cutaneous at 17:30 on day 1 and once at 08:00 on day 2 of the Ganirelix Delayed Puberty Visit

Leuprolide Acetate- Delayed Puberty Leuprolide Visit

Intervention Type DRUG

Leuprolide acetate is given at a dose of10 mcg/kg at 0800 on day 2 of the Delayed Puberty Leuprolide Visit

3

Boys with Early Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion

Group Type EXPERIMENTAL

Leuprolide Acetate - Early Puberty Leuprolide Visit

Intervention Type DRUG

Dose of 10 mcg/kg Sub cutaneous once at 0800 on day 2 of the Early Puberty Luprolide Visit

Ganirelix - Early Puberty Ganirelix Visit

Intervention Type DRUG

Dose of 2.5 mcg/kg Sub-cutaneous once at 17:30 on day 1 of the Early Puberty Ganirelix Visit and once at 08:00 on day 2 of the Early Puberty Ganirelix Visit

4

Boys with Delayed Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion

Group Type EXPERIMENTAL

Ganirelix - Delayed Puberty Ganirelix Visit

Intervention Type DRUG

Ganirelix is administered at a dose of 2.5 mcg/kg sub cutaneous at 17:30 on day 1 and once at 08:00 on day 2 of the Ganirelix Delayed Puberty Visit

Leuprolide Acetate- Delayed Puberty Leuprolide Visit

Intervention Type DRUG

Leuprolide acetate is given at a dose of10 mcg/kg at 0800 on day 2 of the Delayed Puberty Leuprolide Visit

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Leuprolide Acetate - Early Puberty Leuprolide Visit

Dose of 10 mcg/kg Sub cutaneous once at 0800 on day 2 of the Early Puberty Luprolide Visit

Intervention Type DRUG

Ganirelix - Early Puberty Ganirelix Visit

Dose of 2.5 mcg/kg Sub-cutaneous once at 17:30 on day 1 of the Early Puberty Ganirelix Visit and once at 08:00 on day 2 of the Early Puberty Ganirelix Visit

Intervention Type DRUG

Ganirelix - Delayed Puberty Ganirelix Visit

Ganirelix is administered at a dose of 2.5 mcg/kg sub cutaneous at 17:30 on day 1 and once at 08:00 on day 2 of the Ganirelix Delayed Puberty Visit

Intervention Type DRUG

Leuprolide Acetate- Delayed Puberty Leuprolide Visit

Leuprolide acetate is given at a dose of10 mcg/kg at 0800 on day 2 of the Delayed Puberty Leuprolide Visit

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Leuprolide Injection Lupron Lupron SQ Lupron Injection Leuprolide SQ Ganirelix SQ Ganirelix Acetate Ganirelix SQ Ganirelix Acetate Leuprolide Injection Lupron Lupron SQ Lupron Injection Leuprolide SQ

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Early Puberty Children who have early puberty may participate in this study. Children must be between 6 and 10 years of age and be healthy with the exception of having early puberty. For early puberty, girls should have had the onset of breast development prior to 8 years of age and boys should have the onset of pubic hair growth or genital growth prior to 9 years of age.

Exclusion Criteria

Early Puberty Children with known genetic disorders, chronic medical conditions requiring the use of steroids, and use of medication for puberty within the last 3 months are excluded.

Delayed Puberty Children with known genetic disorders with the exception of possible hypogonadotropic hypogonadism, chronic medical conditions requiring the use of steroids, and use of medication for puberty within the last 3 months are excluded.

\-
Minimum Eligible Age

6 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Michigan

OTHER

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Carol Foster

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Carol M Foster, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah, Department of Pediatric Endocrinology

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Utah Diabetes Center

Salt Lake City, Utah, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

5M01RR000064

Identifier Type: NIH

Identifier Source: secondary_id

View Link

05-3125

Identifier Type: -

Identifier Source: org_study_id