Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00392756|
Recruitment Status : Recruiting
First Posted : October 26, 2006
Last Update Posted : September 1, 2017
The purpose of the study is to examine how Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) affect reproductive hormones. These disorders are caused by a defect in Gonadotropin Releasing Hormone (GnRH) secretion. GnRH is a hormone released by a small gland in the brain called the hypothalamus. When GnRH is released, it signals another gland in the brain, the pituitary, to secrete the reproductive hormones that influence testosterone levels and sperm production.
This study involves a detailed evaluation and 8-24 hours stay at the hospital.
In this study, males ages 16 and older with IHH have a detailed evaluation which involves an overnight study at the hospital. Some men (18 years and older) may continue on to receive treatment with pulsatile GnRH. This treatment replaces the hormone which is absent in IHH and results in normalized testosterone and typically is effective in developing fertility.
|Condition or disease||Intervention/treatment||Phase|
|Kallmann Syndrome Hypogonadotropic Hypogonadism GnRH Deficiency||Drug: gonadotropin releasing hormone (GnRH)||Not Applicable|
The specific aims of this study are:
- To identify men and women with hypogonadotropic hypogonadism and to define the spectrum of abnormalities in GnRH secretion in these patients.
- To study the physiology and control of the reproductive system in the human male and female.
- To determine the relationship between glucose metabolism and testosterone levels in men with hypogonadotropic hypogonadism.
- To characterize the neuroendocrine and metabolic phenotype of subjects with IHH and use this information to make genotype-phenotype correlations.
Despite variability in the triggers, timing, and pace of sexual maturity between species, all species utilize the final pathway of hypothalamic secretion of GnRH to initiate and maintain the reproductive axis. Thus, GnRH is required for reproductive competence in the human. The classic studies of Knobil and his colleagues in the 1970s clearly demonstrated that pulsatile release of GnRH from the hypothalamus is a prerequisite for physiologic gonadotrope function, with continuous stimulation resulting in a paradoxical decrease in gonadotrope responsiveness.
Absence, decreased frequency or decreased amplitude of pulsatile GnRH release results in the clinical syndrome of hypogonadotropic hypogonadism (HH). Deficient GnRH secretion may occur in isolation (idiopathic hypogonadotropic hypogonadism [IHH]), in association with anosmia (Kallmann syndrome [KS]) or as a result of a variety of structural and functional lesions of the hypothalamic-pituitary axis. The phenotypic expression of GnRH deficiency in the human demonstrates considerable heterogeneity, suggesting that patients with IHH and KS may represent part of a spectrum of isolated GnRH deficiency as opposed to representing discrete diagnostic subsets.
Defining the physiology of GnRH is critical to understanding the clinical heterogeneity of isolated GnRH deficiency. This protocol will utilize the disease model of HH to increase our understanding of the physiology of GnRH secretion. Examining the baseline characteristics of patients with isolated GnRH deficiency allows the determination of the normal requirements for endogenous GnRH secretion in the human.
Recent studies have revealed an association between hyperinsulinemia and low testosterone levels in men. This finding has been demonstrated in normal physiological conditions as well as in insulin resistant states. However, the causal nature and directionality of this relationship is not yet understood. Specifically, do lower testosterone levels cause insulin resistance resulting in hyperinsulinemia or vice versa. Because insulin resistance is an important risk factor for cardiovascular disease as well as type 2 diabetes, it is important to investigate this relationship for the implications it may have for prevention of and therapeutic interventions for these disorders.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||800 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Role of Gonadotropin Pulsations in the Reversal of Hypogonadotropic Hypogonadism|
|Study Start Date :||April 1989|
|Estimated Primary Completion Date :||March 2018|
|Estimated Study Completion Date :||March 2019|
No Intervention: off treatment
Subjects undergo the baseline evaluation off treatment
Experimental: GnRH Treatment
Subjects receive long term pulsatile GnRH therapy
Drug: gonadotropin releasing hormone (GnRH)
pulsatile GnRH is delivered to adult men (18+ yrs) via portable microinfusion pump. A small dose (30 microliters) is delivered subcutaneously every 120 minutes. The initial dose is 25 ng/Kg which is increased until normal serum testosterone levels are achieved.
- endogenous LH secretion pattern [ Time Frame: 8 to 24 hours ]
- testicular volume [ Time Frame: up to 2 years ]
- sperm count [ Time Frame: up to 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00392756
|Contact: Ravikumar Balasubramanian, MD, PhD||617-726-8432||RBALASUBRAMANIAN@mgh.harvard.edu|
|Contact: Kathryn Salnikov, BSfirstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114-2696|
|Contact: Ravikumar Balasumbramanian, MD, PhD 617-726-8432 RBALASUBRAMANIAN@mgh.harvard.edu|
|Contact: Kathryn Salnikov, BS 617-726-1309 email@example.com|
|Principal Investigator: William Crowley, MD|
|Principal Investigator:||William F Crowley, Jr., MD||Massachusetts General Hospital|