Clinical trial NCT03315325: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sterility, Reproductive
Keywords: Aging
Lead sponsor: Quaid-e-Azam University
Sponsor class: OTHER
First posted: 2017-10-20
Enrollment: 15
Sex: MALE
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

• Age

Exclusion Criteria:

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

Primary outcomes:
measure: To investigate the basal function of KISS1R on GnRH neurons through serum LH and testosterone during aging in men
timeFrame: Two blood samples at 30 minutes interval before kisspeptin injection were obtained from all the groups to determine basal levels for LH and testosterone.
measure: 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
timeFrame: One blood sample from all individuals were obtained after 30 minutes of post kisspeptin injection for measuring a change in LH and testosterone.
measure: 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
timeFrame: One blood sample from all individuals were obtained after 60 minutes of post kisspeptin injection for measuring a change in LH and testosterone.
measure: 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
timeFrame: One blood sample from all individuals were obtained after 90 minutes of post kisspeptin injection for measuring a change in LH and testosterone.
measure: 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
timeFrame: One blood sample from all individuals were obtained after 120 minutes of post kisspeptin injection for measuring a change in LH and testosterone.
Secondary outcomes:
Other outcomes:
Locations:
city: Islamabad
country: Pakistan
facility: Quaid-i-Azam University
Study officials:
affiliation: Quaid-i-Azam University
name: Shahab
role: STUDY_CHAIR
References:
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.
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.
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.
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.