Delayed PubertyEarly Phase 1NCT00734279
Follicle-Stimulating Hormone (FSH) and the Onset of Puberty
A Early Phase 1 study testing Leuprolide Acetate - Early Puberty Leuprolide Visit, Ganirelix - Early Puberty Ganirelix Visit and Ganirelix - Delayed Puberty Ganirelix Visit in people with Delayed Puberty and Precocious Puberty, run by University of Utah at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 6 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Delayed Puberty, Precocious Puberty
- What is being tested?
- Leuprolide Acetate - Early Puberty Leuprolide Visit, Ganirelix - Early Puberty Ganirelix Visit and Ganirelix - Delayed Puberty Ganirelix Visit
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to Dec 2010
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
- Inclusion Criteria for Delayed Puberty Children who have late (delayed) puberty may participate in this study. Children must be between 12 and 17 years of age and be healthy with the exception of having late puberty. In order to have late puberty, boys and girls should have short stature compared to their family with at least one year delay in bone age as determined by bone age x-ray and/or have the onset of secondary sexual characteristics (breast and pubic hair growth) at 12 years of age or later for a girl or 13 years of age or later for a boy.
Who cannot join
- 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.
- -
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the detailed description
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
- Delayed Puberty, Precocious Puberty
- Being tested
- Leuprolide Acetate - Early Puberty Leuprolide Visit, Ganirelix - Early Puberty Ganirelix Visit, Ganirelix - Delayed Puberty Ganirelix Visit, Leuprolide Acetate- Delayed Puberty Leuprolide Visit
- Keywords
- Puberty, Delayed, Early, Precocious, Peripubertal, Gonadotropin, FSH, LH
- Medical subject headings
- Puberty, Delayed, Puberty, Precocious
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Leuprolide Acetate - Early Puberty Leuprolide VisitDrug
Also called Leuprolide Injection, Lupron, Lupron SQ, Lupron Injection
Dose of 10 mcg/kg Sub cutaneous once at 0800 on day 2 of the Early Puberty Luprolide Visit
Ganirelix - Early Puberty Ganirelix VisitDrug
Also called Ganirelix SQ, Ganirelix Acetate
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
Ganirelix - Delayed Puberty Ganirelix VisitDrug
Also called Ganirelix SQ, Ganirelix Acetate
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 VisitDrug
Also called Leuprolide Injection, Lupron, Lupron SQ, Lupron Injection
Leuprolide acetate is given at a dose of10 mcg/kg at 0800 on day 2 of the Delayed Puberty Leuprolide Visit
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Girls with Early Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion Receives: Drug: Leuprolide Acetate - Early Puberty Leuprolide Visit; Drug: Ganirelix - Early Puberty Ganirelix Visit |
| 2 | Experimental | Girls with Delayed Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion Receives: Drug: Ganirelix - Delayed Puberty Ganirelix Visit; Drug: Leuprolide Acetate- Delayed Puberty Leuprolide Visit |
| 3 | Experimental | Boys with Early Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion Receives: Drug: Leuprolide Acetate - Early Puberty Leuprolide Visit; Drug: Ganirelix - Early Puberty Ganirelix Visit |
| 4 | Experimental | Boys with Delayed Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion Receives: Drug: Ganirelix - Delayed Puberty Ganirelix Visit; Drug: Leuprolide Acetate- Delayed Puberty Leuprolide Visit |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the ability of the GnRH antagonist, ganirelix, to suppress nocturnal gonadotropin secretion in peripubertal boys and girls
Measured: Sample analysis is conducted after the leuprolide portion of the study and the ganirelix portion of the study have been completed for the first 6 patients
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startMar 2006
- Primary completionNov 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Delayed PubertyStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- University of Michigan, University of Chicago
- Responsible party
- Principal investigator, Carol Foster, University of Utah
- Investigators
- Carol M Foster, MD, Principal investigator, University of Utah, Department of Pediatric Endocrinology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734279
- Sponsor's protocol ID
- 05-3125
- Other IDs
- 5M01RR000064
- Status last verified
- Dec 2017
- First submitted
- 23 Jul 2008
- Last updated
- 26 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Follicle-Stimulating Hormone (FSH) and the Onset of Puberty
- ClinicalTrials.gov ID
- NCT00734279
- Acronym / sponsor ID
- 05-3125
- Conditions
- Delayed Puberty, Precocious Puberty
- Keywords
- Puberty, Delayed, Early, Precocious, Peripubertal, Gonadotropin, FSH, LH
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- University of Michigan, University of Chicago
- Study start
- Mar 2006
- Primary completion
- Nov 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Leuprolide Acetate - Early Puberty Leuprolide Visit, Drug: Ganirelix - Early Puberty Ganirelix VisitGirls with Early Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion |
| 2 | Experimental | Drug: Ganirelix - Delayed Puberty Ganirelix Visit, Drug: Leuprolide Acetate- Delayed Puberty Leuprolide VisitGirls with Delayed Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion |
| 3 | Experimental | Drug: Leuprolide Acetate - Early Puberty Leuprolide Visit, Drug: Ganirelix - Early Puberty Ganirelix VisitBoys with Early Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion |
| 4 | Experimental | Drug: Ganirelix - Delayed Puberty Ganirelix Visit, Drug: Leuprolide Acetate- Delayed Puberty Leuprolide VisitBoys with Delayed Puberty receive ganirelix and leuprolide acetate to determine effect of ganirelix on gonadotropin secretion |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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.
- Inclusion Criteria for Delayed Puberty Children who have late (delayed) puberty may participate in this study. Children must be between 12 and 17 years of age and be healthy with the exception of having late puberty. In order to have late puberty, boys and girls should have short stature compared to their family with at least one year delay in bone age as determined by bone age x-ray and/or have the onset of secondary sexual characteristics (breast and pubic hair growth) at 12 years of age or later for a girl or 13 years of age or later for a boy.
Key exclusion criteria (3 listed)
- 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.
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Leuprolide Acetate - Early Puberty Leuprolide VisitAlso: Leuprolide Injection, Lupron, Lupron SQ, Lupron InjectionDose of 10 mcg/kg Sub cutaneous once at 0800 on day 2 of the Early Puberty Luprolide Visit | Drug | 1, 3 |
| Ganirelix - Early Puberty Ganirelix VisitAlso: Ganirelix SQ, Ganirelix AcetateDose 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 | Drug | 1, 3 |
| Ganirelix - Delayed Puberty Ganirelix VisitAlso: Ganirelix SQ, Ganirelix AcetateGanirelix 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 | Drug | 2, 4 |
| Leuprolide Acetate- Delayed Puberty Leuprolide VisitAlso: Leuprolide Injection, Lupron, Lupron SQ, Lupron InjectionLeuprolide acetate is given at a dose of10 mcg/kg at 0800 on day 2 of the Delayed Puberty Leuprolide Visit | Drug | 2, 4 |
Primary outcome
Determine the ability of the GnRH antagonist, ganirelix, to suppress nocturnal gonadotropin secretion in peripubertal boys and girls
Time frame: Sample analysis is conducted after the leuprolide portion of the study and the ganirelix portion of the study have been completed for the first 6 patients
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carol M Foster, MD principal investigator
University of Utah, Department of Pediatric Endocrinology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Leuprolide Acetate - Early Puberty Leuprolide Visit, Ganirelix - Early Puberty Ganirelix Visit and Ganirelix - Delayed Puberty Ganirelix Visit in people with Delayed Puberty and Precocious Puberty, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the ability of the GnRH antagonist, ganirelix, to suppress nocturnal gonadotropin secretion in peripubertal boys and girls (time frame: Sample analysis is conducted after the leuprolide portion of the study and the ganirelix portion of the study have been completed for the first 6 patients). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2017.