Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT01500447 |
| Other study ID # |
120049 |
| Secondary ID |
12-E-0049 |
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 25, 2012 |
Study information
| Verified date |
March 12, 2024 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
NIEHS Join A Study Recruitment Group |
| Phone |
(855) 696-4347 |
| Email |
myniehs[@]nih.gov |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background:
- During puberty, children begin to develop into adults. Problems with the hormones released
during puberty can affect the reproductive system. Some people have low hormone levels that
severely delay or prevent puberty. Others start puberty abnormally early. Other people may
have a normal puberty but develop reproductive disorders later in life. Researchers want to
study people with reproductive disorders to learn more about how these disorders may be
inherited.
Objectives:
- To learn how reproductive system disorders may be inherited.
Eligibility:
- People with one of the following problems:
- Abnormally early puberty
- Abnormally late or no puberty
- Normal puberty with hormonal problems that develop later in life
- People who have not yet had puberty but have symptoms that indicate low hormone levels.
Design:
- Participants will provide a blood sample for testing. They will complete a questionnaire
about their symptoms. They will also have a scratch-and-sniff test to study any problems
with their ability to smell.
- Participant medical records will be reviewed. Participants will also provide a family
medical history.
- Family members of those in the study may be invited to participate.
- Treatment will not be provided as part of this study....
Description:
The key initiating factors for reproductive development remain among the great mysteries of
pediatric and reproductive endocrinology. The onset of puberty is initiated by pulsatile
secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The neuroendocrine
events leading to increased GnRH secretion and the resultant onset of puberty remain largely
unknown.
Isolated deficiency of GnRH results in the rare clinical syndrome of idiopathic
hypogonadotropic hypogonadism (IHH), where decreased secretion of GnRH results in impaired
gonadotropin secretion. The resultant hypogonadism presents with delayed, incomplete, or
absent sexual maturation. Human and animal models have identified a number of genes
responsible for IHH, but more than half of patients with clinical evidence of the disorder do
not have a detectable mutation. In addition, there is significant clinical heterogeneity
among affected individuals, including members of the same family harboring the same
mutations. Careful human phenotyping of such patients and families has expanded our
understanding of this spectrum of disorders to include oligo-digenic inheritence, as well as
reversibility of the condition, and has provided insight into developmental pathways involved
in the ontogeny of GnRH neurons. In particular, hypogonadotropic hypogonadism (HH) exists
along a genetic and phenotypic spectrum that includes milder forms of GnRH dysregulation,
precocious and delayed puberty, and onset of reproductive dysfunction after puberty.
Genetic analysis of subjects with unknown mutations is likely to yield important insights
into additional pathways involved in the regulation of GnRH secretion. Here, we propose a
genetic investigation of subjects with IHH to characterize further the phenotypic effect of
previously described genetic variants, as well as to identify novel genes involved in
congenital GnRH deficiency. We will use both candidate gene and whole exome approaches, as
well as linkage analysis.
This protocol will utilize the disease model of IHH to increase our understanding of the
physiology of GnRH secretion, including the neuroendocrine regulation of GnRH pulsatility.
Examining the genetic characteristics of subjects with isolated GnRH deficiency will reveal
insights into the mechanisms underlying the reawakening of the hypothalamic-pituitary-gonadal
axis at puberty, providing opportunities for new diagnostic capabilities and therapeutic
interventions for disorders of puberty and fertility.
