Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism

NCT ID: NCT00493961

Last Updated: 2022-07-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-01-31

Study Completion Date

2009-11-17

Brief Summary

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Men with Idiopathic Hypogonadotropic Hypogonadism (IHH) lack a hormone called gonadotropin releasing hormone (GnRH). This hormone is important for starting puberty, maintaining testosterone levels, and fertility. The purpose of this study is to research the effects of treating IHH men with GnRH for 7 days.

Detailed Description

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Despite variability in the triggers, timing, and pace of sexual maturity between species, all species utilize the final pathway of hypothalamic secretion of gonadotropin releasing hormone (GnRH) to initiate and maintain the reproductive axis. Thus, GnRH is required for reproductive competence in the human. The classic studies from the 1970s clearly demonstrate that pulsatile release of GnRH from the hypothalamus is a prerequisite for physiologic gonadotrope function. Absence, decreased frequency or decreased amplitude of pulsatile GnRH release results in the clinical syndrome of hypogonadotropic hypogonadism (HH). The phenotypic expression of GnRH deficiency in the human demonstrates considerable heterogeneity. Defining the physiology of GnRH is critical to understanding the clinical heterogeneity of isolated GnRH deficiency and its comparison to other conditions resulting in hypogonadotropic hypogonadism (HH). The overall goal of this protocol is to investigate the neuroendocrine control of reproduction and specifically the physiology and pathophysiology of GnRH secretion and action in the human male.

Subjects will be selected from a group of adult men (18-65 years)based on the demonstration of a low testosterone level (\<100 ng/dL) in association with low or inappropriately normal gonadotropin levels. All patients will undergo an initial assessment that includes an overnight 12-hour frequent blood sampling study to determine their degree of endogenous GnRH secretion. Following the overnight evaluation, subjects will have daily outpatient visits for 7 consecutive days when they will receive a GnRH bolus followed by 2hrs of blood sampling.

Conditions

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Kallmann Syndrome Idiopathic Hypogonadotropic Hypogonadism GnRH Deficiency

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Interventions

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gonadotropin releasing hormone (GnRH)

Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of idiopathic hypogonadotropic hypogonadism (IHH) or Kallmann syndrome (KS)Adult male 18-65 years of age
* Serum testosterone \<100 ng/dL
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Stephanie B. Seminara, MD

Chief, Reproductive Endocrine Unit; Professor of Medicine, Harvard Medical School; Director, Harvard Reproductive Endocrine Sciences Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Seminara B Stephanie, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Science. 1978 Nov 10;202(4368):631-3. doi: 10.1126/science.100883.

Reference Type BACKGROUND
PMID: 100883 (View on PubMed)

Seminara SB, Hayes FJ, Crowley WF Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocr Rev. 1998 Oct;19(5):521-39. doi: 10.1210/edrv.19.5.0344. No abstract available.

Reference Type BACKGROUND
PMID: 9793755 (View on PubMed)

Arimura A, Kastin AJ, Gonzalez-Barcena D, Siller J, Weaver RE, Schally AV. Disappearance of LH-releasing hormone in man as determined by radioimmunoassay. Clin Endocrinol (Oxf). 1974 Oct;3(4):421-5. doi: 10.1111/j.1365-2265.1974.tb02812.x. No abstract available.

Reference Type BACKGROUND
PMID: 4609640 (View on PubMed)

Pimstone B, Epstein S, Hamilton SM, LeRoith D, Hendricks S. Metabolic clearance and plasma half disappearance time of exogenous gonadotropin releasing hormone in normal subjects and in patients with liver disease and chronic renal failure. J Clin Endocrinol Metab. 1977 Feb;44(2):356-60. doi: 10.1210/jcem-44-2-356.

Reference Type BACKGROUND
PMID: 320223 (View on PubMed)

Clarke IJ, Cummins JT. The temporal relationship between gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. Endocrinology. 1982 Nov;111(5):1737-9. doi: 10.1210/endo-111-5-1737. No abstract available.

Reference Type BACKGROUND
PMID: 6751801 (View on PubMed)

Karsch FJ, Bowen JM, Caraty A, Evans NP, Moenter SM. Gonadotropin-releasing hormone requirements for ovulation. Biol Reprod. 1997 Feb;56(2):303-9. doi: 10.1095/biolreprod56.2.303.

Reference Type BACKGROUND
PMID: 9116125 (View on PubMed)

Spratt DI, O'Dea LS, Schoenfeld D, Butler J, Rao PN, Crowley WF Jr. Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone. Am J Physiol. 1988 May;254(5 Pt 1):E658-66. doi: 10.1152/ajpendo.1988.254.5.E658.

Reference Type BACKGROUND
PMID: 3129947 (View on PubMed)

Hayes FJ, McNicholl DJ, Schoenfeld D, Marsh EE, Hall JE. Free alpha-subunit is superior to luteinizing hormone as a marker of gonadotropin-releasing hormone despite desensitization at fast pulse frequencies. J Clin Endocrinol Metab. 1999 Mar;84(3):1028-36. doi: 10.1210/jcem.84.3.5579.

Reference Type BACKGROUND
PMID: 10084591 (View on PubMed)

Hoffman AR, Crowley WF Jr. Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone. N Engl J Med. 1982 Nov 11;307(20):1237-41. doi: 10.1056/NEJM198211113072003.

Reference Type BACKGROUND
PMID: 6813732 (View on PubMed)

Whitcomb RW, Crowley WF Jr. Clinical review 4: Diagnosis and treatment of isolated gonadotropin-releasing hormone deficiency in men. J Clin Endocrinol Metab. 1990 Jan;70(1):3-7. doi: 10.1210/jcem-70-1-3. No abstract available.

Reference Type BACKGROUND
PMID: 2403572 (View on PubMed)

Filippi G. Klinefelter's syndrome in Sardinia. Clinical report of 265 hypogonadic males detected at the time of military check-up. Clin Genet. 1986 Oct;30(4):276-84.

Reference Type BACKGROUND
PMID: 3791676 (View on PubMed)

Fromantin M, Gineste J, Didier A, Rouvier J. [Impuberism and hypogonadism at induction into military service. Statistical study]. Probl Actuels Endocrinol Nutr. 1973 May 3;16:179-99. No abstract available. French.

Reference Type BACKGROUND
PMID: 4147392 (View on PubMed)

Filicori M, Butler JP, Crowley WF Jr. Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion. J Clin Invest. 1984 Jun;73(6):1638-47. doi: 10.1172/JCI111370.

Reference Type BACKGROUND
PMID: 6427277 (View on PubMed)

Narasimha Rao P, Moore PH Jr. Synthesis of new steroid haptens for radioimmunoassay. Part I. 15beta-Carboxyethylmercaptotestosterone-bovine serum albumin conjugate. Measurement of testosterone in male plasma without chromatography. Steroids. 1976 Jul;28(1):101-9. doi: 10.1016/0039-128x(76)90129-x.

Reference Type BACKGROUND
PMID: 960143 (View on PubMed)

Groome NP, Illingworth PJ, O'Brien M, Pai R, Rodger FE, Mather JP, McNeilly AS. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996 Apr;81(4):1401-5. doi: 10.1210/jcem.81.4.8636341.

Reference Type BACKGROUND
PMID: 8636341 (View on PubMed)

Landy H, Schneyer AL, Whitcomb RW, Crowley WF Jr. Validation of highly specific and sensitive radioimmunoassays for lutropin, follitropin, and free alpha subunit in unextracted urine. Clin Chem. 1990 Feb;36(2):340-4.

Reference Type BACKGROUND
PMID: 2105862 (View on PubMed)

Pitteloud N, Thambundit A, Dwyer AA, Falardeau JL, Plummer L, Caronia LM, Hayes FJ, Lee H, Boepple PA, Crowley WF Jr. Role of seminiferous tubular development in determining the FSH versus LH responsiveness to GnRH in early sexual maturation. Neuroendocrinology. 2009;90(3):260-8. doi: 10.1159/000245383. Epub 2009 Oct 15.

Reference Type RESULT
PMID: 19829004 (View on PubMed)

Sykiotis GP, Hoang XH, Avbelj M, Hayes FJ, Thambundit A, Dwyer A, Au M, Plummer L, Crowley WF Jr, Pitteloud N. Congenital idiopathic hypogonadotropic hypogonadism: evidence of defects in the hypothalamus, pituitary, and testes. J Clin Endocrinol Metab. 2010 Jun;95(6):3019-27. doi: 10.1210/jc.2009-2582. Epub 2010 Apr 9.

Reference Type RESULT
PMID: 20382682 (View on PubMed)

Related Links

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http://www.massgeneral.org/reproendo/pages/reu_study_subject.htm

Clinical research studies of the Reproductive Endocrine Unit at the Massachusetts General Hospital. Click here for more information about this study: Effects of Seven Days of Exogenous Pulsatile GnRH Treatment...

Other Identifiers

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U54HD028138

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U54HD028138-447

Identifier Type: -

Identifier Source: org_study_id

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