Calciotropic Effects After hCG Stimulation Test

Hypogonadism, Male Clinical Trial

Official title:

Calciotropic Effects After hCG Stimulation Test

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03254641
• Other study ID #: H-17004362
• Status: Completed
• Start date: April 1, 2017
• Est. completion date: October 6, 2020

Study information

• Verified date: October 2020
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

We have in a pilot study found that serum calcium levels change in response to hCG stimulation test. We observed that serum calcium level measured at baseline and 72 hours after hCG stimulation were different in men with gonadal insufficiency referred for this stimulation test. Now we want to investigate a large cohort of men referred for hCG stimulation test due to suspected impaired gonadal function.

Description:

Introduction:

hCG signals through the LHCGR receptor and is know to stimulate testosterone production. hCG stimulation tests are therefore used to evaulate the capacity of the testis to respond to LH/hCG and thereby determine the degree og gonadal insufficiency and need for testosterone supplementation. Some groups have found LHCRG in extragondal tissues indicating a direct effect of hCG/LH outside the gonads. We noticed that some men with gonadal insuffciency had a low calcium level after hCG stimulation test. Now we would like to investigate whether this putative effect on calcium homeostasis of hCG is due to a direct effect or an indirect effect through testosterone or other sex steroids that also change in response to hCG stimulation. Moreover, we would like to clarify whether the chnage in calcium is compensated by classical regulators such as PTH, 1,25OH2D3, calcitonin, phosphate, CTX, alkaline phosphatase or other factors.

Aim of study:

The purpose of this study is to describe changes in calcium and calciotropic hormones after hCG stimulation test

DESIGN This is a prospective observational study

Patients and methods 100 men referred for hCG stimulation test due to suspected gonadal insuffciency age 18-60 years at Department of growth and reproduction, Rigshospitalet

Exclusion criteria are

intake of high dose calcium (above 1 mg daily) Known Disorders related to calcium metabolism, hypercalcemia, Granulomatous disease such as Wegener, tuberculosis, etc,

SAMPLE SIZE CALCULATION AND STATISTICS By using a test level of 5% (level of significance), power of 80% and at least 100 men completing the trial will enable us to detect a change in calcium of 10%, and a change in serum PTH of 30%.

SCREENING AND TIME COURSE Men referred for hCG stimulation test at ourDepartment will be screened for eligibility to the study. Those who meet the criteria for participation will be informed, and if they consent allocated to the study.

Each person will have one blood sampling performed prior to the test and 72 and 96 hours after the test.

Blood samples Venus blood is drawn preoperatively before hCG administration, 72 and 96 hours after. Serum will be send for analysis within 45 minutes and the rest frozen within 1 hour and will be stored at minus 20 degrees celsius until analysis.

OUTCOME MEASUREMENTS

Primary endpoints

•Changes in total, albumin corrected and ionized calcium

Main Secondary endpoints

• Changes in PTH

• Changes in 1,25OH2D3

• Changes in Phosphate

• Changes in FGF23

• Changes in Calcitonin

• Changes in LHCGR in serum

• Changes in Cortisol

• Changes in total and free testosterone

• Changes in total and free estradiol

• Changes in kidney function (GFR/creatinin)

• Changes in gonadotropins

• Changes in 25OHD, 24,25OH2D3

• Changes in serum concentrations of putative regulators and downstream signals osteocalcin, osteopontin, RANKL, osteoprotegerin (OPG), alpha Klotho, Sclerostin and IGF-1.

Temporal changes in serum level of binding proteins. differences for vitamin D binding protein, albumin and sex hormone binding globulin.

Predefined subgroups orchiectomized men/ bilaterally irradiated testis High versus low baseline estradiol/testosterone Low/high calcium/PTH baseline

ANALYSIS AND INTERVENTION

Reproductive hormones and growth factors will be analysed at dept. of GR, Rigshospitalet. Other serum analyses will be analysed at Department of clinical biochemistry, and Aarhus Kommune Hospital

ETHICS AND SIDE EFFECTS All the patients will have full-filled their investigation, before they are invited to the study. They will be informed of potential adverse effects, and they can leave the trial at any point without any consequences. This study poses no additional risk to the patients except for the blood samples as everything else is according to standard clinical practice.

PUBLICATION OF RESULTS All results, positive or negative will be submitted to peer reviewed scientific journals. Data will successively be obtained and transferred to a statistical database.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: October 6, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• men aged 18-60 years referred for hCG stimulation test due to previous treatment for testis cancer

Exclusion Criteria:

• high intake calcium

• know disorders in calcium homeostasis

Related Conditions & MeSH terms

• Hypogonadism
• Hypogonadism, Male

Intervention

Drug:
• human chorionic gonadotropin
5000 IE times one

Locations

Country	Name	City	State
Denmark	Department of Growth and Reproduction, Rigshospitalet	Copenhagen
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Martin Blomberg Jensen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in total, albumin corrected or ionized calcium	mmol/l	72 and 96 hours after hCG injection
Secondary	PTH		72 and 96 hours after hCG injection
Secondary	1,25OH2D3		72 and 96 hours after hCG injection
Secondary	Phosphate		72 and 96 hours after hCG injection
Secondary	cortisol		72 and 96 hours after hCG injection
Secondary	total and free testosterone		72 and 96 hours after hCG injection
Secondary	total and free estradiol		72 and 96 hours after hCG injection
Secondary	albumin, Shbg, VDBP		72 and 96 hours after hCG injection
Secondary	25OHD or 24,25OH2D3		72 and 96 hours after hCG injection
Secondary	bone factors such as CTX, osteocalcin, RANKL, FGF23		72 and 96 hours after hCG injection
Secondary	LHCGR	in serum	72 and 96 hours after hCG injection
Secondary	kidney function	eGFR/creatinine	72 and 96 hours after hCG injection