<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/NCT04484051</url>
  </required_header>
  <id_info>
    <org_study_id>GAP</org_study_id>
    <nct_id>NCT04484051</nct_id>
  </id_info>
  <brief_title>Growth Hormone Study in Adults With Prader-Willi Syndrome</brief_title>
  <acronym>GAP</acronym>
  <official_title>Growth Hormone Study in Adults With Prader-Willi Syndroom</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Erasmus Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Foundation for Prader-Willi Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Prader-Willi Fonds</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Erasmus Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective of this study is to measure the effect of growth hormone (GH) treatment&#xD;
      on physical and psychosocial health in adults with Prader-Willi syndrome. Adults with PWS who&#xD;
      have not been treated with GH during the past three years and who will start with GH&#xD;
      treatment as part of regular patient care will be asked for informed consent to participate&#xD;
      in this open-label prospective cohort study. We hypothesize that growth hormone treatment&#xD;
      will improve the physical and psychosocial health.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVES:&#xD;
&#xD;
      To measure the effect of GHt on physical and psychosocial health in adults with PWS.&#xD;
&#xD;
      The primary endpoint is change in lean body mass (LBM (kg)) as assessed by Dual Energy X-ray&#xD;
      Absorptiometry (DEXA) scan. Secondary endpoints are total fat mass, bone density, physical&#xD;
      health and psychosocial health. Also the occurrence of side-effects will be assessed. Only&#xD;
      data that are collected as part of regular patient care will be used.&#xD;
&#xD;
      STUDY DESIGN:&#xD;
&#xD;
      Open-label prospective cohort study.&#xD;
&#xD;
      STUDY POPULATION:&#xD;
&#xD;
      Adults with PWS who have not been treated with GH during the past three years and who will&#xD;
      start with GHt as part of regular patient care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">March 24, 2023</start_date>
  <completion_date type="Anticipated">October 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2026</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in lean body mass</measure>
    <time_frame>36 months</time_frame>
    <description>Change in lean body mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in fat mass</measure>
    <time_frame>36 months</time_frame>
    <description>Change in fat mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in bone density</measure>
    <time_frame>36 months</time_frame>
    <description>Change in bone density (in T-score) as measured by Dual Energy X-ray Absorptiometry scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in physical strength</measure>
    <time_frame>36 months</time_frame>
    <description>Change in physical strenght as measured by handgrip dynamometer and sit-to-stand tests</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in laboratory measurements</measure>
    <time_frame>36 months</time_frame>
    <description>Changes in the following laboratory measurements:&#xD;
Glycosylated hemoglobin (mmol/mol)&#xD;
Total cholesterol (mmol/L)&#xD;
Low-density lipoprotein cholesterol (mmol/L)&#xD;
High-density lipoprotein cholesterol (mmol/L)&#xD;
Insulin-like growth factor 1 (nmol/L)&#xD;
Free thyroxine 4 (pmol/L)&#xD;
Luteinizing hormone (U/I)&#xD;
Follicle stimulating hormone (U/I)&#xD;
Estradiol or testosterone (nmol/L)&#xD;
Sex hormone binding globulin (nmol/L)&#xD;
Aspartate transaminase (U/L)&#xD;
Alanine transaminase (U/L)&#xD;
Alkaline phosphatase (U/L)&#xD;
Gamma glutamyl transpeptidase (U/L)&#xD;
Total bilirubin (micromol/L)&#xD;
Lactate dehydrogenase (U/L)&#xD;
Urea (mmol/L)&#xD;
Creatinine (micromol/L)&#xD;
Hemoglobin (mmol/L)&#xD;
Hematocrit (L/L)&#xD;
Mean corpuscular volume (fL)&#xD;
Leukocytes (10^9/L)&#xD;
Thrombocytes (10^9/L)&#xD;
25-OH vitamin D (nmol/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in psychosocial functioning</measure>
    <time_frame>36 months</time_frame>
    <description>Change in psychosocial functioning as estimated with the Adult Behaviour Checklist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in caregiver burden</measure>
    <time_frame>36 months</time_frame>
    <description>Change in caregiver burden as estimated with the Zarit Burden Interview</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in weight and waist-hip ratio</measure>
    <time_frame>36 months</time_frame>
    <description>Change in weight (in kg) and waist-hip ratio</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in blood pressure</measure>
    <time_frame>36 months</time_frame>
    <description>Change in blood pressure (in mmHg)</description>
  </other_outcome>
  <other_outcome>
    <measure>Occurence of side-effects</measure>
    <time_frame>36 months</time_frame>
    <description>Occurrence of side-effects</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Prader-Willi Syndrome</condition>
  <arm_group>
    <arm_group_label>Routine clinical care with Genotropin treatment</arm_group_label>
    <description>Data collection throughout routine clinical care with subcutaneous injections Genotropin, 0.6-0.8 mg/day. Participants start with 0.2 mg/day and the dose increases with 0.2 mg/day per month to a maximum dose of 0.6-0.8 mg/day.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Adults with PWS who have not been treated with GH during the past three years and who will&#xD;
        start with GHt as part of regular patient care.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient is diagnosed with Prader-Willi syndrome (genetically confirmed)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non cooperative behaviour&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Known malignancies&#xD;
&#xD;
          -  Poorly controlled diabetes (HbA1c &gt; 64 mmol/mol (8%))&#xD;
&#xD;
          -  Untreated obstructive sleep apnea (apnea-hypopnea index &gt; 5)&#xD;
&#xD;
          -  Body mass index above 40 kg/m2&#xD;
&#xD;
          -  Upper-airway obstruction of any cause&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Laura de Graaff, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Erasmus MC, University Medical Center Rotterdam</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Laura de Graaff, MD, PhD</last_name>
    <phone>0031618843010</phone>
    <email>l.degraaff@erasmusmc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Trui van Essen, MD</last_name>
    <phone>0031658869674</phone>
    <email>g.vanessen@erasmusmc.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Erasmus MC, University Medical Center Rotterdam</name>
      <address>
        <city>Rotterdam</city>
        <state>Zuid-Holland</state>
        <zip>3015GD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <contact>
      <last_name>Laura de Graaff, MD, PhD</last_name>
      <phone>0031618843010</phone>
      <email>l.degraaff@erasmusmc.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <removed_countries>
    <country>Australia</country>
  </removed_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Erasmus Medical Center</investigator_affiliation>
    <investigator_full_name>dr. Laura C. G. de Graaff-Herder</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Prader-Willi syndrome</keyword>
  <keyword>Growth hormone</keyword>
  <keyword>Body composition</keyword>
  <keyword>Cardiovascular disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prader-Willi Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The individual participant data has not been finalized yet. The investigators intent to share the full anonymized dataset, study protocol and statistical analysis plan upon request after publication of the results. Informed consent forms will not be shared.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>The data will become available around begin 2027 (after publication of the results). The data will be available for 15 years.</ipd_time_frame>
    <ipd_access_criteria>Upon reasonable request.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT04484051
org study id: GAP
nct id: NCT04484051
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The overall objective of this study is to measure the effect of growth hormone (GH) treatment
      on physical and psychosocial health in adults with Prader-Willi syndrome. Adults with PWS who
      have not been treated with GH during the past three years and who will start with GH
      treatment as part of regular patient care will be asked for informed consent to participate
      in this open-label prospective cohort study. We hypothesize that growth hormone treatment
      will improve the physical and psychosocial health.
OBJECTIVES:

      To measure the effect of GHt on physical and psychosocial health in adults with PWS.

      The primary endpoint is change in lean body mass (LBM (kg)) as assessed by Dual Energy X-ray
      Absorptiometry (DEXA) scan. Secondary endpoints are total fat mass, bone density, physical
      health and psychosocial health. Also the occurrence of side-effects will be assessed. Only
      data that are collected as part of regular patient care will be used.

      STUDY DESIGN:

      Open-label prospective cohort study.

      STUDY POPULATION:

      Adults with PWS who have not been treated with GH during the past three years and who will
      start with GHt as part of regular patient care.
observational model: Cohort
time perspective: Prospective
measure: Change in lean body mass
time frame: 36 months
description: Change in lean body mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan
measure: Change in fat mass
time frame: 36 months
description: Change in fat mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan
measure: Change in bone density
time frame: 36 months
description: Change in bone density (in T-score) as measured by Dual Energy X-ray Absorptiometry scan
measure: Change in physical strength
time frame: 36 months
description: Change in physical strenght as measured by handgrip dynamometer and sit-to-stand tests
measure: Change in laboratory measurements
time frame: 36 months
description: Changes in the following laboratory measurements:
Glycosylated hemoglobin (mmol/mol)
Total cholesterol (mmol/L)
Low-density lipoprotein cholesterol (mmol/L)
High-density lipoprotein cholesterol (mmol/L)
Insulin-like growth factor 1 (nmol/L)
Free thyroxine 4 (pmol/L)
Luteinizing hormone (U/I)
Follicle stimulating hormone (U/I)
Estradiol or testosterone (nmol/L)
Sex hormone binding globulin (nmol/L)
Aspartate transaminase (U/L)
Alanine transaminase (U/L)
Alkaline phosphatase (U/L)
Gamma glutamyl transpeptidase (U/L)
Total bilirubin (micromol/L)
Lactate dehydrogenase (U/L)
Urea (mmol/L)
Creatinine (micromol/L)
Hemoglobin (mmol/L)
Hematocrit (L/L)
Mean corpuscular volume (fL)
Leukocytes (10^9/L)
Thrombocytes (10^9/L)
25-OH vitamin D (nmol/L)
measure: Change in psychosocial functioning
time frame: 36 months
description: Change in psychosocial functioning as estimated with the Adult Behaviour Checklist
measure: Change in caregiver burden
time frame: 36 months
description: Change in caregiver burden as estimated with the Zarit Burden Interview
measure: Change in weight and waist-hip ratio
time frame: 36 months
description: Change in weight (in kg) and waist-hip ratio
measure: Change in blood pressure
time frame: 36 months
description: Change in blood pressure (in mmHg)
measure: Occurence of side-effects
time frame: 36 months
description: Occurrence of side-effects
arm group label: Routine clinical care with Genotropin treatment
description: Data collection throughout routine clinical care with subcutaneous injections Genotropin, 0.6-0.8 mg/day. Participants start with 0.2 mg/day and the dose increases with 0.2 mg/day per month to a maximum dose of 0.6-0.8 mg/day.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laura de Graaff, MD, PhD
role: Principal Investigator
affiliation: Erasmus MC, University Medical Center Rotterdam
last name: Laura de Graaff, MD, PhD
phone: 0031618843010
email: l.degraaff@erasmusmc.nl
last name: Trui van Essen, MD
phone: 0031658869674
email: g.vanessen@erasmusmc.nl
facility: 
contact: 
country: Netherlands
country: Australia
responsible party type: Principal Investigator
investigator affiliation: Erasmus Medical Center
investigator full name: dr. Laura C. G. de Graaff-Herder
investigator title: MD, PhD
mesh term: Prader-Willi Syndrome
mesh term: Syndrome
sharing ipd: Yes
ipd description: The individual participant data has not been finalized yet. The investigators intent to share the full anonymized dataset, study protocol and statistical analysis plan upon request after publication of the results. Informed consent forms will not be shared.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: The data will become available around begin 2027 (after publication of the results). The data will be available for 15 years.
ipd access criteria: Upon reasonable request.