Trial record 18 of 3528 for:    Open Studies | "Endocrine System Diseases"

Hormonal Regulation of Puberty and Fertility

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01511588
First received: January 13, 2012
Last updated: August 19, 2014
Last verified: July 2014
  Purpose

Background:

- The body produces gonadotropin-releasing hormone (GnRH) about every 2 hours. GnRH travels through the bloodstream to the pituitary gland, where it stimulates the gland to produce hormones called gonadotropins. These hormones stimulate the testicles or ovaries. The testicles produce testosterone and develop sperm. The ovaries produce estrogen and prepare for ovulation. Normal estrogen and testosterone levels are required for puberty. Some people, however, have either low levels or total lack of GnRH. This can cause problems with puberty and fertility. Researchers want to study people with low or no GnRH to better understand how it affects puberty and fertility.

Objectives:

- To study disorders of GnRH production.

Eligibility:

  • Adult men and women at least 18 years of age with low or no gonadotropin levels.
  • Adolescents between 14 and 18 years of age with low or no gonadotropin levels.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
  • Participants will have tests to look at their hormone levels. Blood samples may be collected after taking different drugs, including insulin and cortisone. A 24-hour urine sample will be collected.
  • Participants will have imaging studies to look at bone and brain development. They will also have ultrasounds of the kidneys, abdomen, and reproductive organs.
  • Tests of smell and hearing will be used to look for abnormalities in these senses.

Condition
Endocrine Disease
Infertility
Hypogonadism
Amenorrhea
Adolescents

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Hormonal Regulation of Puberty and Fertility

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The main outcome is the identification of novel GnRH secretory patterns or non-reproductive phenotypic characteristics in individuals representing the complete spectrum of idiophatic hypogonadism.

Secondary Outcome Measures:
  • Secondary outcomes are the recognition of specific pubertal phenotypes, as well as discovery of the roles of newly identified genes contributing to IHH in GnRH development and biology, for those subjects who also enroll in our genetics protocol.

Estimated Enrollment: 800
Study Start Date: December 2011
Detailed 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. GnRH secretion is fully active during the neonatal period, quiescent throughout most of childhood, and is reactivated at the time of puberty to induce sexual maturation and subsequent fertility. 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. In addition, non-reproductive phenotypes of this spectrum have been identified in some individuals, including anosmia, auditory defects, skeletal and renal anomalies.

Defining the physiology of GnRH is critical to understanding the clinical heterogeneity of isolated GnRH deficiency, particularly in light of emerging gene discoveries that elucidate genotype-phenotype correlations. Careful human phenotyping of patients with mutations in genes known to cause IHH has provided insight into developmental pathways involved in the ontogeny of GnRH neurons, but the neuroendocrine regulation of this system is not well understood.

Here, we propose the addition of the NIH as the second site to an existing protocol at Massachusetts General Hospital to phenotypically characterize subjects with IHH. We plan to admit males and females 14 years of age or older with clinical signs suggestive of IHH for comprehensive phenotyping to include neuroendocrine profiling via an LH pulsatility study, as well as identification of other non-reproductive findings. Combining our effort with the established protocol and recruitment mechanisms at MGH will allow us to maximize the number of subjects with this rare disorder that can be evaluated.

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, as well as other unknown aspects of GnRH biology, which may be illuminated through the non-reproductive characteristics of these patients. Examining the baseline 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.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Since hypogonadotropic hypogonadism is a rare condition, with an incidence of 1/10,000 to 1/86,000 for isolated GnRH deficiency (34, 35), this protocol remains open to enrollment so that we may study all subjects that are both qualified and interested in participating.

Males or females who are greater than or equal to 14 years old with clinical findings of HH as outlined above will be included. In certain circumstances, a patient under the age of 14 years may be considered for baseline evaluation if there is sufficient evidence suggestive of HH, such as any two of the following: anosmia, history of cryptorchidism or microphallus.

EXCLUSION CRITERIA:

-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).
  • Patients who are taking medications known to cause HH, such as corticosteroids or continuous opiate administration.
  • Pregnancy or lactation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01511588

Contacts
Contact: Angela Delaney, M.D. (301) 496-3025 delaneya@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Angela Delaney, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01511588     History of Changes
Other Study ID Numbers: 120050, 12-CH-0050
Study First Received: January 13, 2012
Last Updated: August 19, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Kallmann Syndrome
Delayed Puberty
GnRH Deficiency
Infertility
Hypogonadotropic Hypogonadism
Amenorrhea
Hypogonadism

Additional relevant MeSH terms:
Infertility
Hypogonadism
Amenorrhea
Endocrine System Diseases
Genital Diseases, Male
Genital Diseases, Female
Gonadal Disorders
Menstruation Disturbances
Pathologic Processes

ClinicalTrials.gov processed this record on September 22, 2014