<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/NCT03775993</url>
  </required_header>
  <id_info>
    <org_study_id>2016-004580-39</org_study_id>
    <nct_id>NCT03775993</nct_id>
  </id_info>
  <brief_title>Treatment of GHD Associated With CHF</brief_title>
  <official_title>Treatment of Growth Hormone Deficiency Associated With Chronic Heart Failure: A Randomized, Double-Blind, Placebo-Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federico II University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federico II 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aim of the current study is to assess the cardiovascular effects of GH replacement therapy in&#xD;
      patients with coexisting GHD and CHF&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multiple anabolic deficiencies are common in chronic heart failure (CHF) and identify&#xD;
      subgroups of patients with higher mortality. Apart from CHF, GH deficiency (GHD) per se&#xD;
      increases cardiovascular mortality in the general population and low IGF-1 levels in the&#xD;
      general population predict the development of ischemic heart disease and CHF. GHD modifies&#xD;
      cardiac size and function, through a reduction in both myocardial growth and cardiac&#xD;
      performance. The investigators therefore completed 2 studies aimed at evaluating the clinical&#xD;
      status, neurohormonal parameters, exercise capacity, vascular reactivity, and left&#xD;
      ventricular architecture and function in patients with GHD and CHF, at baseline and after 6&#xD;
      months of GH replacement therapy. They subsequently extended the observation period up to 48&#xD;
      months. At 6-months, GH replacement therapy improved clinical status and exercise capacity,&#xD;
      as shown by a significant reduction of the Minnesota living with heart failure questionnaire&#xD;
      score, increased peak oxygen consumption and exercise duration, and flow mediated&#xD;
      vasodilation of the brachial artery. No major adverse events were reported in the patients&#xD;
      receiving GH.&#xD;
&#xD;
      However, the encouraging results of these studies are limited by the lack of a double-blind,&#xD;
      placebo-controlled design, insofar as the investigators performed a randomized controlled,&#xD;
      single-blind study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 1, 2019</start_date>
  <completion_date type="Anticipated">March 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of peak oxygen consumption (peak VO2)</measure>
    <time_frame>1 year</time_frame>
    <description>According to previous observations, the investigators set a target increase of peak VO2 in the treated arm at 3 ml/kg/min at the end of the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Hospitalizations</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>End-systolic LV volumes</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NT-proBNP levels</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life score from the Minnesota Living with Heart Failure Questionnaire</measure>
    <time_frame>1 year</time_frame>
    <description>The questionnaire is comprised of 21 physical, emotional and socioeconomic questions that may adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (lower valure) to 5 (upper value) scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The final score is calculated by sum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of Endothelial function (flow-mediated vasodilation)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle strength (handgrip)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Levels of Endothelial Progenitor Cells (EPCs)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Levels of lymphocyte G protein-coupled receptor kinase (GRK)-2</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">64</enrollment>
  <condition>Heart Failure</condition>
  <condition>Growth Hormone Deficiency</condition>
  <arm_group>
    <arm_group_label>GHD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Human growth hormone</intervention_name>
    <description>Administration of growth hormone</description>
    <arm_group_label>GHD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administration of placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. patients of either sex affected by CHF NYHA class I-III, secondary to ischemic or&#xD;
             idiopathic di-lated cardiomyopathy;&#xD;
&#xD;
          2. age range 18-85 years;&#xD;
&#xD;
          3. stable and optimal medical therapy for at least three months prior to randomization,&#xD;
             including ACE inhibitors or AT1 antagonists and beta-blockers (unless untolerated);&#xD;
&#xD;
          4. LV ejection fraction 40% or less and LV end-diastolic dimension 55 mm or more;&#xD;
&#xD;
          5. GH deficiency diagnosed with GHRH + arginine provocative test;&#xD;
&#xD;
          6. signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. inability to perform a bicycle exercise test;&#xD;
&#xD;
          2. poorly controlled diabetes mellitus (HbA1c &gt;8.5) and/or active proliferative or severe&#xD;
             non-proliferative diabetic retinopathy;&#xD;
&#xD;
          3. active and/or history of malignancy;&#xD;
&#xD;
          4. unstable angina or recent myocardial infarction (less than six months);&#xD;
&#xD;
          5. severe liver or kidney disease (serum creatinine levels &gt;2.5 mg/dl&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Antonio Cittadini, Full Professor of Medicine</last_name>
    <phone>+390817464375</phone>
    <email>cittadin@unina.it</email>
  </overall_contact>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>February 13, 2019</last_update_submitted>
  <last_update_submitted_qc>February 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Federico II University</investigator_affiliation>
    <investigator_full_name>Antonio Cittadini</investigator_full_name>
    <investigator_title>Full Professor</investigator_title>
  </responsible_party>
  <keyword>Growth Hormone</keyword>
  <keyword>Placebo</keyword>
  <keyword>Exercise capacity</keyword>
  <keyword>Vascular reactivity</keyword>
  <keyword>LV function</keyword>
  <keyword>Prognosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dwarfism, Pituitary</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03775993
org study id: 2016-004580-39
nct id: NCT03775993
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Aim of the current study is to assess the cardiovascular effects of GH replacement therapy in
      patients with coexisting GHD and CHF
Multiple anabolic deficiencies are common in chronic heart failure (CHF) and identify
      subgroups of patients with higher mortality. Apart from CHF, GH deficiency (GHD) per se
      increases cardiovascular mortality in the general population and low IGF-1 levels in the
      general population predict the development of ischemic heart disease and CHF. GHD modifies
      cardiac size and function, through a reduction in both myocardial growth and cardiac
      performance. The investigators therefore completed 2 studies aimed at evaluating the clinical
      status, neurohormonal parameters, exercise capacity, vascular reactivity, and left
      ventricular architecture and function in patients with GHD and CHF, at baseline and after 6
      months of GH replacement therapy. They subsequently extended the observation period up to 48
      months. At 6-months, GH replacement therapy improved clinical status and exercise capacity,
      as shown by a significant reduction of the Minnesota living with heart failure questionnaire
      score, increased peak oxygen consumption and exercise duration, and flow mediated
      vasodilation of the brachial artery. No major adverse events were reported in the patients
      receiving GH.

      However, the encouraging results of these studies are limited by the lack of a double-blind,
      placebo-controlled design, insofar as the investigators performed a randomized controlled,
      single-blind study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change of peak oxygen consumption (peak VO2)
time frame: 1 year
description: According to previous observations, the investigators set a target increase of peak VO2 in the treated arm at 3 ml/kg/min at the end of the study
measure: Number of Hospitalizations
time frame: 1 year
measure: End-systolic LV volumes
time frame: 1 year
measure: NT-proBNP levels
time frame: 1 year
measure: Quality of life score from the Minnesota Living with Heart Failure Questionnaire
time frame: 1 year
description: The questionnaire is comprised of 21 physical, emotional and socioeconomic questions that may adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (lower valure) to 5 (upper value) scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The final score is calculated by sum.
measure: Evaluation of Endothelial function (flow-mediated vasodilation)
time frame: 1 year
measure: Muscle strength (handgrip)
time frame: 1 year
measure: Evaluation of the Levels of Endothelial Progenitor Cells (EPCs)
time frame: 1 year
measure: Evaluation of the Levels of lymphocyte G protein-coupled receptor kinase (GRK)-2
time frame: 1 year
arm group label: GHD
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Human growth hormone
description: Administration of growth hormone
arm group label: GHD
intervention type: Other
intervention name: Placebo
description: Administration of placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Antonio Cittadini, Full Professor of Medicine
phone: +390817464375
email: cittadin@unina.it
responsible party type: Principal Investigator
investigator affiliation: Federico II University
investigator full name: Antonio Cittadini
investigator title: Full Professor
mesh term: Dwarfism, Pituitary
mesh term: Heart Failure
mesh term: Hormones
sharing ipd: No