Inherited Reproductive Disorders
|First Submitted Date||December 21, 2011|
|First Posted Date||December 28, 2011|
|Last Update Posted Date||December 15, 2017|
|Start Date||December 20, 2011|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures
||The main outcome is the identification of known and novel genetic variants in individuals representing the complete spectrum of idiopathic hypogonadotropic hypogonadism.|
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT01500447 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Inherited Reproductive Disorders|
|Official Title||The Molecular Basis of Inherited Reproductive Disorders|
- 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.
- To learn how reproductive system disorders may be inherited.
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.
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. In collaboration with the Reproductive Endocrine Unit at the Massachusetts General Hospital, we will use both candidate gene and whole exome approaches, as well as linkage analysis. The collaboration will allow for sufficient statistical power to conduct such an investigation.
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.
|Study Design||Observational Model: Family-Based
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries||United States|
|Removed Location Countries||Chile|
|Other Study ID Numbers||120049
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )|
|Study Sponsor||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|
|Collaborators||Massachusetts General Hospital|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||December 13, 2017|