View Clinical Trial (Medical Research Study)
The Molecular Basis of Inherited Reproductive Disorders
| City: |
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Bethesda |
| State: |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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Endocrine Diseases - Genetic Disorder - Infertility - Hypogonadism - Amenorrhea |
| Purpose: |
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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.
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| Study Summary: |
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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.
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| Criteria: |
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- The essential inclusion criteria include:
1. failure to go through a normal, age-appropriate, spontaneous puberty and low sex
steroid levels in the setting of low/normal gonadotropins, or
2. abnormally early development of puberty, or
3. normal puberty with subsequent development of low gonadotropin levels, or
4. pre-pubertal individuals with features suggestive of hypogonadotropic
hypogonadism.
5. Family members: both affected and unaffected family members are strongly
encouraged to participate.
EXCLUSION CRITERIA:
Since hypogonadotropic hypogonadism is a rare condition, this protocol remains
open to enrollment so that we may study all subjects that are both qualified and
interested in participating.
Because HH represents a spectrum, where associated clinical findings may provide
phenotypic clues to the assessment of inheritability and underlying physiology,
exclusion criteria are very limited:
- Patients who have additional pituitary deficiencies, effectively ruling out isolated
GnRH deficiency, whether these deficiencies are congenital or acquired (e.g.
secondary to malignancy, infection, or irradiation).
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| NCT ID: |
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NCT01500447 |
| Primary Contact: |
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Principal Investigator
Angela Delaney, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Angela Delaney, M.D.
Phone: (301) 496-3025
Email: delaneya@mail.nih.gov
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| Backup Contact: |
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N/A |
| Location Contact: |
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Bethesda, Maryland 20892
United States
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 22, 2013 |
| Modifications to this listing: |
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