Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders

This study is currently recruiting participants.
Verified February 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Information provided by (Responsible Party):
William Crowley, Harvard University
ClinicalTrials.gov Identifier:
NCT00494169
First received: June 28, 2007
Last updated: February 19, 2014
Last verified: February 2014

June 28, 2007
February 19, 2014
January 1999
May 2015   (final data collection date for primary outcome measure)
Identification of DNA abnormalities [ Time Frame: 5/2015 ] [ Designated as safety issue: No ]
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Complete list of historical versions of study NCT00494169 on ClinicalTrials.gov Archive Site
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Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders
Molecular Basis of Inherited Reproductive Disorders

The aims of this study are: 1) to identify genes that play a role in human pubertal development and reproduction, 2) to characterize the phenotypic spectrum of patients with these gene defects, and 3) to discern the mode of inheritance for disorders caused by these gene defects. We are specifically interested in genes that cause Kallmann syndrome, idiopathic hypogonadotropic hypogonadism (IHH), precocious (early) puberty, and delayed puberty. Individuals do not have to travel to Boston to participate in this study.

Overview:

Our work is divided into two main areas of investigation:

  1. the discovery of new, yet-undiscovered genes for conditions of early (i.e. precocious) puberty, delayed puberty, absence of pubertal development (i.e. Kallmann syndrome) as well as normal puberty that is accompanied by an altered reproductive system later in life (i.e. hypothalamic amenorrhea in women or very low testosterone levels in men). Identification of new genes requires either a single large family or a collection of smaller families.
  2. a detailed examination of the genes already implicated in causing these conditions.

There are several other important aspects about our program:

  • This analysis will detect DNA abnormalities only in those DNA segments being screened. The turnaround time to process a sample is approximately 6-9 months. We must receive a signed consent form in order to begin analysis on a blood sample.
  • Our laboratory is located in Massachusetts General Hospital, Boston MA and is largely funded by the National Institutes of Health. We are a research laboratory and not a CLIA certified clinical laboratory.
  • Even if a patient is the only member of his/her family affected by one of the conditions mentioned above, obtaining blood samples on other family members, including parents and siblings is often important to our work.
  • It is every individual's responsibility to notify the research team he/she would like to obtain research results. The patient must sign a second consent form before receiving such information.

Study Procedures and Risks

  • You will be asked to give approximately 3-5 tablespoons of blood for this research project. There is a risk of bruising and a very small amount of bleeding associated with blood drawing.
  • You will be asked to fill out a medical history checklist, indicating the presence or absence of clinical features that may be associated with abnormalities in pubertal development.
  • Since absence of puberty is sometimes associated with limited or no smell ability, you may be asked to try to identify the odors in a scratch and sniff test. This will take about 15 minutes.
  • Your family history can give us clues to determine how your condition was inherited. Therefore, a detailed family history, at least back to your grandparents will be obtained by a researcher.

Benefits:

There are no direct benefits to you from participation in this study. Some genes for this condition are known, other genes have yet to be discovered. If this study discovers what genes are responsible, it will help to further the understanding of this disorder. It is possible that the genetic cause of your reproductive disorder may be learned. This information can be shared with you at your request.

When contacting us, please include in your message a description of your diagnosis, your pubertal history (age when you hit pubertal hallmarks, e.g., growth spurt; body hair; voice deepening and genital growth for men; menstruation and breast development for women) and your reproductive history.

Observational
Observational Model: Case Control
Time Perspective: Cross-Sectional
Not Provided
Retention:   Samples With DNA
Description:

WBC are transformed into immortalized cell lines.

Non-Probability Sample

Subjects who

  1. fail to go through a normal, age-appropriate, spontaneous puberty, and abnormal hormone levels.
  2. have abnormally early development of puberty (Precocious Puberty) OR
  3. display low gonadotropins in adulthood after having gone through normal pubertal development.

Family members of these patients.

  • Hypogonadism
  • Kallmann Syndrome
  • Puberty, Delayed
  • Puberty, Precocious
  • Hypothalamic Amenorrhea
  • Anosmia
  • GnRH Deficiency
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
5000
May 2015
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Failure to go through a normal, age-appropriate, spontaneous puberty, and abnormal hormone levels.
  • Children with abnormally early development of puberty (Precocious Puberty)
  • Adults who display low gonadotropins in adulthood after having gone through normal pubertal development.
  • Family members of these patients.

Exclusion Criteria:

  • pituitary tumor
  • high prolactin levels
Both
Not Provided
Yes
Contact: Cassandra Buck, CGC, MS 617-726-5526 ReproEndoGenetics@partners.org
Contact: Kayla Sheets, CGC, MS 617-724-2704 ksheets@partners.org
United States
 
NCT00494169
U54HD028138
No
William Crowley, Harvard University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Principal Investigator: William F Crowley, Jr., MD Massachusetts General Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP