Extragonadal Effects of hCG on Calcium Homeostasis

June 11, 2023 updated by: Martin Blomberg Jensen

Novel Extragonadal Effects of Human Chorion Gonadotropin (hCG) on Calcium Homeostasis

A pilot study showed that serum calcium levels and calcium homeostasis change in response to hCG stimulation test. Serum calcium level differed when comparing pretreatment values at baseline with serum levels 72 hours after hCG stimulation in men with gonadal insufficiency referred for this stimulation test. Now we want to investigate whether this change in calcium is due to renal loss or other mechanisms and how the classical regulators of calcium homeostasis respond to hCG in men with impaired gonadal function compared with men having normal gonadal function. Moreover, the observed change in serum calcium implies that hCG also changes Phosphate, PTH and calcitonin and this will be clarified with this study

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Aim To investigate whether human chorionic gonadotropin (hCG) stimulation test changes calcium-phosphate homeostasis in men with normal and impaired testicular function.

The overall purpose of the project is to investigate the importance of human chorion gonadotropin (hCG) for the calcium balance in normal men and men with impaired testicular function.

BACKGROUND AND HYPOTHESES

The Department for Growth and Reproduction has helped to uncover the rising occurrence of early puberty, infertility, polycystic ovarian syndrome and testicular cancer that is worryingly high in large numbers parts of the world (1). These conditions are all governed by the hormonal axis that contains hypothalamus, pituitary gland, and the HPG axis (2). Our hypothesis is, that hCG may be a new regulator of calcium balance. hCG acts like luteinizing hormone (LH) produced by the pituitary gland and stimulates by binding to the LH receptor (LHCGR) production of testosterone in the testicles (3-6). we and others have found that that LHCGR is also located in other tissues than the gonad (7) and we suggest that LH stimulation probably also regulates calcium handling in the kidney. We have observed changes in serum calcium after hCG injection in patients with impaired testicular function, which indicates that the gonads and gonadotropins may be important for calcium and phosphate homeostasis. It is compatible with the fact that it has been shown that ex FSH can regulate bone function (8),and sex hormones are important for calcium absorption and excretion in the kidney (9-11). The latter is interesting because our research suggests that the receptor for the luteinizing hormone and hCG (LHCGR) plays an important role in the kidney, thus enabling a direct effect on calcium and phosphate handling for LHCGR agonists such as LH and hCG.

With this study we want to investigate how hCG influences calcium homeostasis and subsequently other extragonadal organs by analyzing serum and urine from men with normal and impaired gonadal function

DESIGN This is a prospective intervention study in cases and controls

Patients and methods 10-15 men referred for hCG stimulation test due to suspected gonadal insufficiency after curative treatment for testicular cancer with orchiectomy, irradiation or chemotherapy age 18-80 years at Department of growth and reproduction, Rigshospitalet and 10-15 men with normal reproductive function

SAMPLE SIZE CALCULATION AND STATISTICS By using a test level of 5% (level of significance), power of 80% and at least 10 normal men and 10 men with impaired gonadal function completing the trial will enable us to detect a change in serum calcium of 6%, PTH of 25% and a change in serum Phosphate of 15%.

SCREENING AND TIME COURSE Men referred for hCG stimulation test at our Department 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.Venus blood is drawn before hCG administration, 2,8,24 72 and 120 hours after injection. Spot urine samples will be delivered and ECG monitoring will be performed at all time points. All men will be fasting for baseline, 2 hours, 24, 72 and 120 hours sampling. Serum will be send for analysis within 40 minutes and the rest frozen within 1 hour and will be stored at minus 80 degrees celsius until analysis.

Biostatistical analysis each individual's samples will be normalized by division of the value of the given parameter (for instance calcium or phosphate) to the baseline samples drawn before the intervention.

Hence, samples from each volunteer at the different timepoints will be normalized with the individual's own baseline values before the administration of hCG. Initially, paired Student t tests will be used to compare changes in serum or urine by comparing baseline levels with the different time points. Unpaired Student t tests will be used to compare controls and men with gonadal insufficiency at all time points. Moreover, the presumable effect of multiple testing will be tested afterwards by using ANOVA followed by a post hoc Dunnett's /SIDAK multiple comparison test. All data will after indexation to baseline levels be shown as mean ± SEM. Differences were considered statistically significant when P ≤ 0.05.

Predefined subgroups Changes in calcium and phosphate will be analyzed according to baseline sex steroids and delta sex steroids, LHCGR, BMI, GFR, PTH

Principal Investigator: Li Juel Mortensen Sponsor: Martin Blomberg Jensen

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
      • Copenhagen, Denmark, 2100
        • Department of Growth and Reproduction, Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria: to be either

  • a man with normal reproductive function
  • or a man with known impaired gonadal function
  • more than 18 years of age and less than 80 years of age

Exclusion Criteria:

  • presence of current serious diseases
  • or presence of disease requiring constant and lifelong treatment with chemotherapy or other toxic drugs
  • Men treated with testosterone who do not stop their treatment while being part of the study,

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: human chorion gonadotropin
Pregnyl, hCG, 5000 IU times one im.
Drug: human chorionic gonadotropin
a single injection of a standard dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Serum calcium
Time Frame: 2,8,24, 72,120 hours
changes albumin corrected calcium, ionized calcium, total calcium
2,8,24, 72,120 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
urinary calcium and phosphate excretion
Time Frame: 2,8,24, 72,120 hours
calcium and phosphate clearance and fractional excretion
2,8,24, 72,120 hours
serum Phosphate
Time Frame: 2,8,24, 72,120 hours
changes in serum phosphate
2,8,24, 72,120 hours

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
vitamin D metabolites
Time Frame: 2,8,24, 72,120 hours
25OHD, 1,25OH2D3, 24,25OH2D3
2,8,24, 72,120 hours
calcitonin
Time Frame: 2,8,24, 72,120 hours
changes in serum calcitonin
2,8,24, 72,120 hours
Cortisol
Time Frame: 2,8,24, 72,120 hours
Changes in serum cortisol
2,8,24, 72,120 hours
adrenal steroidogenesis
Time Frame: 2,8,24, 72,120 hours
all measurable steroids part of steroidogenesis by LCMS
2,8,24, 72,120 hours
sex steroids
Time Frame: 2,8,24, 72,120 hours
total and free calculated levels of sex steroids including T/LH
2,8,24, 72,120 hours
reproductive hormones
Time Frame: 2,8,24, 72,120 hours
AMH, Inhibin B, FSH, including InhB/FSH
2,8,24, 72,120 hours
change in adipocyte function
Time Frame: 2,8,24, 72,120 hours
biomarkers in serum of adipocyte function, browning, differentiation, insulin, glucose, HB1AC etc
2,8,24, 72,120 hours
LHCGR
Time Frame: 2,8,24, 72,120 hours
serum LHCGR may change
2,8,24, 72,120 hours
regulators of calcium homeostasis
Time Frame: 2,8,24, 72,120 hours
serum calcitonin, FGF23, interferons, prostaglandins
2,8,24, 72,120 hours
Kidney function
Time Frame: 2,8,24, 72,120 hours
changes in GFR, creatinine, Urea, pH, HCO3
2,8,24, 72,120 hours
Electrocardiogram
Time Frame: 2,8,24,72,120 hours
changes in QT, corrected QY or QRS
2,8,24,72,120 hours
adipocyte function
Time Frame: 2,8,24,72,120 hours
changes in serum lipid or cholesterol or adipocyte function markers
2,8,24,72,120 hours
liver function
Time Frame: 2,8,24,72,120 hours
changes in albumin and hepatic binding proteins
2,8,24,72,120 hours
bone function
Time Frame: 2,8,24,72,120 hours
changes in bone markers such as CTX, osteocalcin and endocrine bone factors RANKL, OPG, RANK, sclerostin
2,8,24,72,120 hours
serum PTH
Time Frame: 2,8,24,72,120 hours
changes in serum PTH
2,8,24,72,120 hours
urinary excretion of steroids
Time Frame: 2,8,24,72,120 hours
cortisol and sex steroids
2,8,24,72,120 hours
Cardiovascular biomarkers
Time Frame: 2,8,24,72,120 hours
ANP and BNP
2,8,24,72,120 hours
glucose homeostasis
Time Frame: 2,8,24,72,120 hours
insulin, glucose, c-peptid, HB1AC, HOMA, Quicki
2,8,24,72,120 hours
incretin hormones
Time Frame: 2,8,24,72,120 hours
glucagon, and GLP-1
2,8,24,72,120 hours
electrolytes
Time Frame: 2,8,24,72,120 hours
Magnesium, potassium, sodium
2,8,24,72,120 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Martin Blomberg Jensen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Martin blomberg Jensen, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 6, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 25, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 1, 2018

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2016-003546-84

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Normally we share the data through an official danish Databank handling all these things

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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