<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03286517</url>
  </required_header>
  <id_info>
    <org_study_id>QuaideAzamU</org_study_id>
    <nct_id>NCT03286517</nct_id>
  </id_info>
  <brief_title>Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys.</brief_title>
  <official_title>Changes in the Responsiveness of the Hypothalamic-pituitary-gonadal (HPG) Axis to Kisspeptin-10 Administration During Pubertal Transition in Boys</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ghulam Nabi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Quaid-e-Azam University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The specific objective of this study was to investigate the sensitivity of Kisspeptin&#xD;
      receptor 1 (KISS1R) by determining the responsiveness of GnRH neuron to kisspeptin&#xD;
      administration across the pubertal stages and adult group through measuring plasma LH&#xD;
      (luteinizing hormone) and testosterone concentrations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      No studies in humans are available regarding KISS1R signalling that, whether expression of&#xD;
      the KISS1 or KISS1R sensitivity increases during the pubertal transition in boys. Kisspeptin&#xD;
      regulates HPG (hypothalamic pituitary gonadal) axis by secreting GnRH that acts on the&#xD;
      pituitary gonadotrophs to secrete LH and FSH. But in contrast to pubertal period, juvenile&#xD;
      period kisspeptin pulsatility is reduced, that leads to low GnRH pulsatility and low level of&#xD;
      plasma LH, FSH and testosterone. The objective of this study was to determine the response of&#xD;
      exogenous kisspeptin in various juvenile stages up to puberty and also in the adults by&#xD;
      measuring the level of plasma LH and testosterone. This study would help us to determine that&#xD;
      whether there is any link between the increased sensitivity of kisspeptin signalling and&#xD;
      puberty onset?, Or at what Tanner stage pre pubertal boys enter into puberty.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 26, 2014</start_date>
  <completion_date type="Actual">March 5, 2015</completion_date>
  <primary_completion_date type="Actual">August 8, 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>All the groups were injected with exogenous IV kisspeptin according to the body weight.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>All the participants were told for injecting the kisspeptin.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>To investigate the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration across the pubertal stages and adult group through measuring plasma luteinizing hormone and testosterone concentrations</measure>
    <time_frame>A time frame for each individual was 3 hours. Kisspeptin-10 was injected intravenously and the blood samples were collected at 30 minutes intervals for 30 minutes pre and 2 hours post kisspeptin-10 injection through cannula.</time_frame>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Reproductive Physiological Phenomena</condition>
  <arm_group>
    <arm_group_label>Tanner Stage I</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 9.5 µg/BW.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tanner Stage II</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 11.50 µg/BW.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tanner Stage III</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 12.67 µg/BW.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tanner Stage IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 15.11 µg/BW.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tanner stage V</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 20.5 µg/BW.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adult Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 1 µg/kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)</intervention_name>
    <description>A neurohormone</description>
    <arm_group_label>Adult Group</arm_group_label>
    <arm_group_label>Tanner Stage I</arm_group_label>
    <arm_group_label>Tanner Stage II</arm_group_label>
    <arm_group_label>Tanner Stage III</arm_group_label>
    <arm_group_label>Tanner Stage IV</arm_group_label>
    <arm_group_label>Tanner stage V</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Boys were classified into 5 different Tanner stages (I-V) according to the criteria of&#xD;
             Feingold D. In Atlas of physical diagnosis. Pediatric endocrinology. 2nd ed.&#xD;
             Philadelphia. WB Saunders; 1992, pp. 16-19. For comparison, adult men were also&#xD;
             recruited.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals with chronic illness or disorder, i.e. hepatic and renal complications,&#xD;
             epilepsy, pneumonia, asthma, orchitis, hernia, cryptorchidism, mental retardation,&#xD;
             etc. were excluded from this study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>children were classified into five pubertal stages called Tanner stages on the basis of a genital examination by a physician.</gender_description>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Muhammad Shahab, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Quaid-i-Azam University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quaid-i-Azam University</name>
      <address>
        <city>Islamabad</city>
        <zip>45320</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <reference>
    <citation>Mead EJ, Maguire JJ, Kuc RE, Davenport AP. Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor, G protein-coupled receptor 54, to atherosclerosis-prone vessels. Endocrinology. 2007 Jan;148(1):140-7. doi: 10.1210/en.2006-0818. Epub 2006 Oct 5.</citation>
    <PMID>17023533</PMID>
  </reference>
  <results_reference>
    <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.</citation>
    <PMID>21976724</PMID>
  </results_reference>
  <results_reference>
    <citation>Jayasena CN, Nijher GM, Chaudhri OB, Murphy KG, Ranger A, Lim A, Patel D, Mehta A, Todd C, Ramachandran R, Salem V, Stamp GW, Donaldson M, Ghatei MA, Bloom SR, Dhillo WS. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab. 2009 Nov;94(11):4315-23. doi: 10.1210/jc.2009-0406. Epub 2009 Oct 9.</citation>
    <PMID>19820030</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>September 13, 2017</last_update_submitted>
  <last_update_submitted_qc>September 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Quaid-e-Azam University</investigator_affiliation>
    <investigator_full_name>Ghulam Nabi</investigator_full_name>
    <investigator_title>Mr.</investigator_title>
  </responsible_party>
  <keyword>Puberty, Sexuality</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual response to kisspeptin administration without disclosing the identity of an individual can be shared with other researchers.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>I have already completed the study and can share the data. It will be available in the form of research paper along with the supplementary materials.</ipd_time_frame>
    <ipd_access_criteria>Will be available on journal website after publication or we can share personally.</ipd_access_criteria>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Any information required can be provided</doc_type>
      <doc_url>http://www.qau.edu.pk/profile.php?id=802001</doc_url>
      <doc_comment>Prof. Muhammad Shahab will provide the information upon request.</doc_comment>
    </study_doc>
  </study_docs>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03286517
org study id: QuaideAzamU
nct id: NCT03286517
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The specific objective of this study was to investigate the sensitivity of Kisspeptin
      receptor 1 (KISS1R) by determining the responsiveness of GnRH neuron to kisspeptin
      administration across the pubertal stages and adult group through measuring plasma LH
      (luteinizing hormone) and testosterone concentrations.
No studies in humans are available regarding KISS1R signalling that, whether expression of
      the KISS1 or KISS1R sensitivity increases during the pubertal transition in boys. Kisspeptin
      regulates HPG (hypothalamic pituitary gonadal) axis by secreting GnRH that acts on the
      pituitary gonadotrophs to secrete LH and FSH. But in contrast to pubertal period, juvenile
      period kisspeptin pulsatility is reduced, that leads to low GnRH pulsatility and low level of
      plasma LH, FSH and testosterone. The objective of this study was to determine the response of
      exogenous kisspeptin in various juvenile stages up to puberty and also in the adults by
      measuring the level of plasma LH and testosterone. This study would help us to determine that
      whether there is any link between the increased sensitivity of kisspeptin signalling and
      puberty onset?, Or at what Tanner stage pre pubertal boys enter into puberty.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: All the groups were injected with exogenous IV kisspeptin according to the body weight.
primary purpose: Basic Science
masking: None (Open Label)
masking description: All the participants were told for injecting the kisspeptin.
measure: To investigate the sensitivity of KISS1R by determining the responsiveness of GnRH neuron to kisspeptin administration across the pubertal stages and adult group through measuring plasma luteinizing hormone and testosterone concentrations
time frame: A time frame for each individual was 3 hours. Kisspeptin-10 was injected intravenously and the blood samples were collected at 30 minutes intervals for 30 minutes pre and 2 hours post kisspeptin-10 injection through cannula.
arm group label: Tanner Stage I
arm group type: Experimental
description: A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 9.5 µg/BW.
arm group label: Tanner Stage II
arm group type: Experimental
description: A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 11.50 µg/BW.
arm group label: Tanner Stage III
arm group type: Experimental
description: A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 12.67 µg/BW.
arm group label: Tanner Stage IV
arm group type: Experimental
description: A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 15.11 µg/BW.
arm group label: Tanner stage V
arm group type: Experimental
description: A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 20.5 µg/BW.
arm group label: Adult Group
arm group type: Experimental
description: A 1ml blood sample was obtained for 30 minutes pre and 120 minutes post-kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany) injection periods at 30 min intervals (-30, 0, 30, 60, 90, 120). The dose was 1 µg/kg.
intervention type: Biological
intervention name: Kisspeptin-10 (metastin 45-54, Calbiochem, Darmstadt, Germany)
description: A neurohormone
arm group label: Adult Group
arm group label: Tanner Stage I
arm group label: Tanner Stage II
arm group label: Tanner Stage III
arm group label: Tanner Stage IV
arm group label: Tanner stage V
criteria: 
gender: Male
gender based: Yes
gender description: children were classified into five pubertal stages called Tanner stages on the basis of a genital examination by a physician.
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Muhammad Shahab, PhD
role: Study Director
affiliation: Quaid-i-Azam University
facility: 
country: Pakistan
citation: Mead EJ, Maguire JJ, Kuc RE, Davenport AP. Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor, G protein-coupled receptor 54, to atherosclerosis-prone vessels. Endocrinology. 2007 Jan;148(1):140-7. doi: 10.1210/en.2006-0818. Epub 2006 Oct 5.
PMID: 17023533
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.
PMID: 21976724
citation: Jayasena CN, Nijher GM, Chaudhri OB, Murphy KG, Ranger A, Lim A, Patel D, Mehta A, Todd C, Ramachandran R, Salem V, Stamp GW, Donaldson M, Ghatei MA, Bloom SR, Dhillo WS. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab. 2009 Nov;94(11):4315-23. doi: 10.1210/jc.2009-0406. Epub 2009 Oct 9.
PMID: 19820030
responsible party type: Sponsor-Investigator
investigator affiliation: Quaid-e-Azam University
investigator full name: Ghulam Nabi
investigator title: Mr.
sharing ipd: Yes
ipd description: Individual response to kisspeptin administration without disclosing the identity of an individual can be shared with other researchers.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: I have already completed the study and can share the data. It will be available in the form of research paper along with the supplementary materials.
ipd access criteria: Will be available on journal website after publication or we can share personally.
study doc: 