<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/NCT02243852</url>
  </required_header>
  <id_info>
    <org_study_id>13/NW/0075</org_study_id>
    <nct_id>NCT02243852</nct_id>
  </id_info>
  <brief_title>Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21)</brief_title>
  <official_title>Evaluation of the Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21) Concentration in Patients With Growth Hormone Deficiency (GHD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Liverpool</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Liverpool</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will recruit healthy controls (who have normal GH production and growth hormone&#xD;
      levels) and patients identified as having GHD, who are deemed eligible for GH replacement&#xD;
      therapy according to NICE guidelines. The patients recruited will have been identified as&#xD;
      starting on GH by their referring clinicians and a decision made on their replacement therapy&#xD;
      prior to their potential enrollment in the study. The study, or its research team, will have&#xD;
      no influence on the decision as to whether a patient will start on GH, or on which of the&#xD;
      many GH formulations that the patients receives. The proposed study is an observational study&#xD;
      to determine how GH affects the plasma levels of Fibroblast growth factor 21 (FGF21) in&#xD;
      response to treatment; and whether the change in FGF21 mirrors the improvement in body&#xD;
      composition/fat deposition. FGF21 is a metabolic regulator that acts on multiple tissues to&#xD;
      coordinate carbohydrate and lipid metabolism and regulate energy balance.&#xD;
&#xD;
      We hypothesize that FGF-21 is expressed and secreted from liver and skeletal muscle in humans&#xD;
      in response to growth hormone administration and that levels may be reduced in patients with&#xD;
      GHD compared with healthy controls. Furthermore, we believe that the beneficial effects of&#xD;
      long-term GH replacement on body composition (reduction in visceral adipose tissue,&#xD;
      subcutaneous adipose tissue and liver fat), on improvement in lipid profiles and on skeletal&#xD;
      muscle mitochondrial function involve GH-induced release of FGF21.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Growth hormone (GH) is involved in controlling people's general health and an underproduction&#xD;
      of growth hormone (growth hormone deficiency or GHD) leads to people feeling generally unwell&#xD;
      and having a lower feeling of well-being and quality of life scores. In addition, the&#xD;
      investigators, and others, have demonstrated people with GHD have reduced muscle and bone&#xD;
      strength and a greater storage of fat, particularly in unfavourable sites such as in the&#xD;
      liver and within the abdomen (visceral fat), rather than beneath the skin (subcutaneous fat).&#xD;
&#xD;
      Treatment of GHD is achieved by administration of GH replacement therapy, given as a once&#xD;
      daily subcutaneous injection, which generally reverses these symptoms. Due to its high cost,&#xD;
      patients are only started on GH replacement depending on the impact that the GHD is having on&#xD;
      their quality of life. Patients must be severely affected to be eligible for replacement&#xD;
      therapy. Patients are screened for quality of life using a well validated, disease specific&#xD;
      questionnaire (AGHDA, Adult Growth hormone deficiency questionnaire) and there are specific&#xD;
      criteria that govern whether a patient with GHD warrants GH replacement and also whether they&#xD;
      continue treatment (NICE guideline: Growth hormone deficiency (adults) - human growth hormone&#xD;
      (TA64)).&#xD;
&#xD;
      This study will specifically determine whether the mechanism of action by which GH exerts its&#xD;
      beneficial effects on metabolism (within adipose tissue and skeletal muscle) involves changes&#xD;
      in serum FGF21 concentrations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <primary_completion_date type="Anticipated">August 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>FGF21</measure>
    <time_frame>6-months</time_frame>
    <description>The primary outcome measure involves differences in serum FGF21 concentration between healthy controls and GHD patients, and changes in FGF21 concentration with GH replacement in patients with GHD</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visceral and subcutaneous fat</measure>
    <time_frame>6-months</time_frame>
    <description>Differences in visceral and subcutaneous fat volume between healthy controls and GHD patients.&#xD;
Changes in visceral and subcutaneous fat volume after 6 months of GH.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Growth Hormone Deficiency</condition>
  <arm_group>
    <arm_group_label>Growth Hormone Deficiency (n=16)</arm_group_label>
    <description>16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement) will be compared with 16 healthy controls. Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be assessed in each of cohort to determine the correlation of FGF21 levels with VAT, SAT and liver fat.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Controls (n=16)</arm_group_label>
    <description>16 healthy controls will be compared with 16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement). Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be measured in all cohorts to determine the correlation of FGF21 levels with VAT, SAT and liver fat.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Growth Hormone Replacement Therapy (n=16)</arm_group_label>
    <description>GHD patients, who are eligible for GH replacement therapy as part of their routine clinical care, according to the National Institute for Clinical Excellence (NICE) recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire score (AGHDA score&gt;11) will be recruited. These patients attend the Joint Endocrine clinic at University Hospital Aintree, Liverpool, and those who are about to commence growth hormone replacement will be asked to participate in this observational study.&#xD;
Anthropometric, biochemical including measurement of FGF21 and MR evaluation will be carried out in patients who are to be treated with GH as part of their routine clinical care immediately prior to GH therapy and after six months of replacement treatment. The type of GH and dose of treatment will be at the discretion of the treating physician. Standard doses will be used and patients will remain under the care of the supervising</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Growth Hormone Replacement Therapy</intervention_name>
    <description>An observational study of patients who are commencing GH replacement as part of their routine NHS clinical care to assess changes in serum FGF21 concentration and determine how these relate to changes in body composition.</description>
    <arm_group_label>Growth Hormone Replacement Therapy (n=16)</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      All patients will have a 15 ml blood sample taken for glucose, insulin, lipid profile and&#xD;
      liver function tests (LFTs). Insulin sensitivity will be measured by HOMA-IR. Plasma&#xD;
      concentrations of FGF-21 will be measured using a commercial ELISA kit (Human FGF-21;&#xD;
      Biovendor, Germany).&#xD;
&#xD;
      16 GHD patients, who are eligible for GH replacement therapy as part of their routine&#xD;
      clinical care, according to the National Institute for Clinical Excellence (NICE)&#xD;
      recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire&#xD;
      score (AGHDA score&gt;11) will also be re-tested following 6-months of growth hormone&#xD;
      replacement therapy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Secondary care clinic University advertisement&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        All evaluations to determine eligibility into the study and for growth hormone replacement&#xD;
        are performed as part of routine clinical care. It should be emphasised that no research&#xD;
        specific screening tests will be performed. Patients deemed eligible for entry into study,&#xD;
        who decline to participate in the research, will still be commenced on growth hormone in&#xD;
        line routine clinical care.&#xD;
&#xD;
        Inclusion criteria: Patients with confirmed GH deficiency who are deemed eligible for GH&#xD;
        replacement as assessed by the AGHDA QOL questionnaire.&#xD;
&#xD;
        Exclusion criteria: Claustrophobia or having significant metal work is a contra-indication&#xD;
        to MRI scanning.&#xD;
&#xD;
        Withdrawal criteria: Patients will be withdrawn from the study if they discontinue their&#xD;
        growth hormone replacement therapy for any clinical reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel J Cuthbertson, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Liverpool</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Daniel J Cuthbertson, PhD</last_name>
    <phone>+441515295911</phone>
    <email>daniel.cuthbertson@liverpool.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Victoria S Sprung, PhD</last_name>
    <phone>+441515295936</phone>
    <email>victoria.sprung@liverpool.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>MARIARC</name>
      <address>
        <city>Liverpool</city>
        <state>Merseyside</state>
        <zip>L69 3GE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Graham J Kemp, PhD</last_name>
      <phone>+44-151-706-4086</phone>
      <email>g.j.kemp@liv.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Graham J Kemp, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Aintree</name>
      <address>
        <city>Liverpool</city>
        <state>Merseyside</state>
        <zip>L9 7AL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniel J Cuthbertson, PhD</last_name>
      <phone>+44 151 529 5911</phone>
      <email>daniel.cuthbertson@liverpool.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Daniel J Cuthbertson, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2014</study_first_posted>
  <last_update_submitted>September 18, 2014</last_update_submitted>
  <last_update_submitted_qc>September 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 19, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Liverpool</investigator_affiliation>
    <investigator_full_name>Daniel Cuthbertson</investigator_full_name>
    <investigator_title>Dr Daniel Cuthbertson</investigator_title>
  </responsible_party>
  <keyword>Growth Hormone Deficiency (GHD)</keyword>
  <keyword>Growth Hormone Replacement Therapy</keyword>
  <keyword>Fibroblast Growth Factor 21 (FGF21)</keyword>
  <keyword>Visceral Fat</keyword>
  <keyword>Subcutaneous Fat</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dwarfism, Pituitary</mesh_term>
    <mesh_term>Endocrine System Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02243852
org study id: 13/NW/0075
nct id: NCT02243852
lead sponsor: 
collaborator: 
has dmc: No
This study will recruit healthy controls (who have normal GH production and growth hormone
      levels) and patients identified as having GHD, who are deemed eligible for GH replacement
      therapy according to NICE guidelines. The patients recruited will have been identified as
      starting on GH by their referring clinicians and a decision made on their replacement therapy
      prior to their potential enrollment in the study. The study, or its research team, will have
      no influence on the decision as to whether a patient will start on GH, or on which of the
      many GH formulations that the patients receives. The proposed study is an observational study
      to determine how GH affects the plasma levels of Fibroblast growth factor 21 (FGF21) in
      response to treatment; and whether the change in FGF21 mirrors the improvement in body
      composition/fat deposition. FGF21 is a metabolic regulator that acts on multiple tissues to
      coordinate carbohydrate and lipid metabolism and regulate energy balance.

      We hypothesize that FGF-21 is expressed and secreted from liver and skeletal muscle in humans
      in response to growth hormone administration and that levels may be reduced in patients with
      GHD compared with healthy controls. Furthermore, we believe that the beneficial effects of
      long-term GH replacement on body composition (reduction in visceral adipose tissue,
      subcutaneous adipose tissue and liver fat), on improvement in lipid profiles and on skeletal
      muscle mitochondrial function involve GH-induced release of FGF21.
Growth hormone (GH) is involved in controlling people's general health and an underproduction
      of growth hormone (growth hormone deficiency or GHD) leads to people feeling generally unwell
      and having a lower feeling of well-being and quality of life scores. In addition, the
      investigators, and others, have demonstrated people with GHD have reduced muscle and bone
      strength and a greater storage of fat, particularly in unfavourable sites such as in the
      liver and within the abdomen (visceral fat), rather than beneath the skin (subcutaneous fat).

      Treatment of GHD is achieved by administration of GH replacement therapy, given as a once
      daily subcutaneous injection, which generally reverses these symptoms. Due to its high cost,
      patients are only started on GH replacement depending on the impact that the GHD is having on
      their quality of life. Patients must be severely affected to be eligible for replacement
      therapy. Patients are screened for quality of life using a well validated, disease specific
      questionnaire (AGHDA, Adult Growth hormone deficiency questionnaire) and there are specific
      criteria that govern whether a patient with GHD warrants GH replacement and also whether they
      continue treatment (NICE guideline: Growth hormone deficiency (adults) - human growth hormone
      (TA64)).

      This study will specifically determine whether the mechanism of action by which GH exerts its
      beneficial effects on metabolism (within adipose tissue and skeletal muscle) involves changes
      in serum FGF21 concentrations.
observational model: Case-Control
time perspective: Prospective
measure: FGF21
time frame: 6-months
description: The primary outcome measure involves differences in serum FGF21 concentration between healthy controls and GHD patients, and changes in FGF21 concentration with GH replacement in patients with GHD
measure: Visceral and subcutaneous fat
time frame: 6-months
description: Differences in visceral and subcutaneous fat volume between healthy controls and GHD patients.
Changes in visceral and subcutaneous fat volume after 6 months of GH.
arm group label: Growth Hormone Deficiency (n=16)
description: 16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement) will be compared with 16 healthy controls. Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be assessed in each of cohort to determine the correlation of FGF21 levels with VAT, SAT and liver fat.
arm group label: Healthy Controls (n=16)
description: 16 healthy controls will be compared with 16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement). Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be measured in all cohorts to determine the correlation of FGF21 levels with VAT, SAT and liver fat.
arm group label: Growth Hormone Replacement Therapy (n=16)
description: GHD patients, who are eligible for GH replacement therapy as part of their routine clinical care, according to the National Institute for Clinical Excellence (NICE) recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire score (AGHDA score>11) will be recruited. These patients attend the Joint Endocrine clinic at University Hospital Aintree, Liverpool, and those who are about to commence growth hormone replacement will be asked to participate in this observational study.
Anthropometric, biochemical including measurement of FGF21 and MR evaluation will be carried out in patients who are to be treated with GH as part of their routine clinical care immediately prior to GH therapy and after six months of replacement treatment. The type of GH and dose of treatment will be at the discretion of the treating physician. Standard doses will be used and patients will remain under the care of the supervising
intervention type: Drug
intervention name: Growth Hormone Replacement Therapy
description: An observational study of patients who are commencing GH replacement as part of their routine NHS clinical care to assess changes in serum FGF21 concentration and determine how these relate to changes in body composition.
arm group label: Growth Hormone Replacement Therapy (n=16)
All patients will have a 15 ml blood sample taken for glucose, insulin, lipid profile and
      liver function tests (LFTs). Insulin sensitivity will be measured by HOMA-IR. Plasma
      concentrations of FGF-21 will be measured using a commercial ELISA kit (Human FGF-21;
      Biovendor, Germany).

      16 GHD patients, who are eligible for GH replacement therapy as part of their routine
      clinical care, according to the National Institute for Clinical Excellence (NICE)
      recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire
      score (AGHDA score>11) will also be re-tested following 6-months of growth hormone
      replacement therapy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Daniel J Cuthbertson, PhD
role: Principal Investigator
affiliation: University of Liverpool
last name: Daniel J Cuthbertson, PhD
phone: +441515295911
email: daniel.cuthbertson@liverpool.ac.uk
last name: Victoria S Sprung, PhD
phone: +441515295936
email: victoria.sprung@liverpool.ac.uk
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Liverpool
investigator full name: Daniel Cuthbertson
investigator title: Dr Daniel Cuthbertson
mesh term: Dwarfism, Pituitary
mesh term: Endocrine System Diseases
mesh term: Hormones