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Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men

Primary Purpose

Sterility, Reproductive

Status
Completed
Phase
Phase 3
Locations
Pakistan
Study Type
Interventional
Intervention
Human kisspeptin-10 (metastin 45-54)
Sponsored by
Quaid-e-Azam University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Sterility, Reproductive focused on measuring Aging

Eligibility Criteria

25 Years - 75 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

• Age

Exclusion Criteria:

  • Hepatic and renal complications
  • Epilepsy
  • Pneumonia
  • Asthma
  • Orchitis
  • Hernia
  • Cryptorchidism
  • Cardiovascular diseases
  • Reproductive disorders
  • Mental retardation

Sites / Locations

  • Quaid-i-Azam University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Adult men

Middle age men

Advance age men

Arm Description

The average age was 25.80±0.37 years and intervention human kisspeptin-10 was administered in single iv bolus dose (1 µg/kg BW). Serial blood samples were collected for 30 min pre and 120 min post-kisspeptin injection periods at 30 min interval.

The average age was 47.00±0.77 years and intervention human kisspeptin-10 was administered in single iv bolus dose (1 µg/kg BW). Serial blood samples were collected for 30 min pre and 120 min post-kisspeptin injection periods at 30 min interval.

The average age was 73.20±0.91 years and intervention human kisspeptin-10 was administered in single iv bolus dose (1 µg/kg BW). Serial blood samples were collected for 30 min pre and 120 min post-kisspeptin injection periods at 30 min interval.

Outcomes

Primary Outcome Measures

To investigate the basal function of KISS1R on GnRH neurons through serum LH and testosterone during aging in men
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 30 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 60 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 90 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 120 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations

Secondary Outcome Measures

Full Information

First Posted
September 30, 2017
Last Updated
October 19, 2017
Sponsor
Quaid-e-Azam University
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1. Study Identification

Unique Protocol Identification Number
NCT03315325
Brief Title
Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men
Official Title
Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis to Kisspeptin-10 Administration in Men
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
August 8, 2014 (Actual)
Primary Completion Date
August 10, 2014 (Actual)
Study Completion Date
March 5, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Quaid-e-Azam University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The present study was designed to assess the responsiveness of the hypothalamic pituitary gonadal axis to kisspeptin administration with increasing age in men.
Detailed Description
Little is known about the involvement of kisspeptin signalling in the causation of senescence-basal modulation of the GnRH-LH unit in any model and particularly in advance age men. The present study was therefore designed to assess the response of hypothalamic pituitary gonadal axis to kisspeptin administration with increasing age in healthy men. Sequential blood samples (2 ml) were obtained for 30 minutes pre and 120 minutes post-kisspeptin injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). Kisspeptin-10 was administered (1 µg/kg BW) as an intravenous bolus, immediately after collecting 0 min sample to assess the response of GnRH neurons to kisspeptin-10 with increasing age in men by determining plasma levels of LH and testosterone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sterility, Reproductive
Keywords
Aging

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Healthy men, 15 in number were selected. These individuals were classified on the basis of their ages in three groups: adult, middle age and advanced aged. Each group comprised of five participants.
Masking
None (Open Label)
Masking Description
There was no masking. Every individual was told about injecting the kisspeptin, however, they were not informed at the time when kisspeptin was injected.
Allocation
Non-Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adult men
Arm Type
Experimental
Arm Description
The average age was 25.80±0.37 years and intervention human kisspeptin-10 was administered in single iv bolus dose (1 µg/kg BW). Serial blood samples were collected for 30 min pre and 120 min post-kisspeptin injection periods at 30 min interval.
Arm Title
Middle age men
Arm Type
Experimental
Arm Description
The average age was 47.00±0.77 years and intervention human kisspeptin-10 was administered in single iv bolus dose (1 µg/kg BW). Serial blood samples were collected for 30 min pre and 120 min post-kisspeptin injection periods at 30 min interval.
Arm Title
Advance age men
Arm Type
Experimental
Arm Description
The average age was 73.20±0.91 years and intervention human kisspeptin-10 was administered in single iv bolus dose (1 µg/kg BW). Serial blood samples were collected for 30 min pre and 120 min post-kisspeptin injection periods at 30 min interval.
Intervention Type
Biological
Intervention Name(s)
Human kisspeptin-10 (metastin 45-54)
Intervention Description
Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) is a potent HPG-axis stimulator and control reproduction.
Primary Outcome Measure Information:
Title
To investigate the basal function of KISS1R on GnRH neurons through serum LH and testosterone during aging in men
Time Frame
Two blood samples at 30 minutes interval before kisspeptin injection were obtained from all the groups to determine basal levels for LH and testosterone.
Title
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 30 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Time Frame
One blood sample from all individuals were obtained after 30 minutes of post kisspeptin injection for measuring a change in LH and testosterone.
Title
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 60 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Time Frame
One blood sample from all individuals were obtained after 60 minutes of post kisspeptin injection for measuring a change in LH and testosterone.
Title
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 90 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Time Frame
One blood sample from all individuals were obtained after 90 minutes of post kisspeptin injection for measuring a change in LH and testosterone.
Title
Changes in the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration after 120 minutes during aging in men through measuring plasma luteinizing hormone and testosterone concentrations
Time Frame
One blood sample from all individuals were obtained after 120 minutes of post kisspeptin injection for measuring a change in LH and testosterone.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: • Age Exclusion Criteria: Hepatic and renal complications Epilepsy Pneumonia Asthma Orchitis Hernia Cryptorchidism Cardiovascular diseases Reproductive disorders Mental retardation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shahab
Organizational Affiliation
Quaid-i-Azam University
Official's Role
Study Chair
Facility Information:
Facility Name
Quaid-i-Azam University
City
Islamabad
ZIP/Postal Code
45320
Country
Pakistan

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
After publishing will be available to all researchers. Additional data will be provided by the corresponding author on request.
Citations:
PubMed Identifier
21470997
Citation
Chan YM, Butler JP, Pinnell NE, Pralong FP, Crowley WF Jr, Ren C, Chan KK, Seminara SB. Kisspeptin resets the hypothalamic GnRH clock in men. J Clin Endocrinol Metab. 2011 Jun;96(6):E908-15. doi: 10.1210/jc.2010-3046. Epub 2011 Apr 6.
Results Reference
result
PubMed Identifier
16174713
Citation
Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA, Bloom SR. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005 Dec;90(12):6609-15. doi: 10.1210/jc.2005-1468. Epub 2005 Sep 20.
Results Reference
result
PubMed Identifier
21632807
Citation
George JT, Veldhuis JD, Roseweir AK, Newton CL, Faccenda E, Millar RP, Anderson RA. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab. 2011 Aug;96(8):E1228-36. doi: 10.1210/jc.2011-0089. Epub 2011 Jun 1.
Results Reference
result
PubMed Identifier
21976724
Citation
Jayasena CN, Nijher GM, Comninos AN, Abbara A, Januszewki A, Vaal ML, Sriskandarajah L, Murphy KG, Farzad Z, Ghatei MA, Bloom SR, Dhillo WS. The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. J Clin Endocrinol Metab. 2011 Dec;96(12):E1963-72. doi: 10.1210/jc.2011-1408. Epub 2011 Oct 5.
Results Reference
result

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Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men

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