<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/NCT02239458</url>
  </required_header>
  <id_info>
    <org_study_id>0388-14-HMO</org_study_id>
    <nct_id>NCT02239458</nct_id>
  </id_info>
  <brief_title>DPP-IV Inhibition Prior to Development of Diabetes in Patients With Cystic Fibrosis</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ram Weiss</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hadassah Medical Organization</source>
  <brief_summary>
    <textblock>
      Cystic fibrosis related diabetes (CFRD) is a common co-morbidity in patients with CF. The&#xD;
      underlying pathophysiology of cystic fibrosis related diabetes (CFRD) is still a matter of&#xD;
      investigation. In addition to localized tissue damage developing similar to that of the&#xD;
      exocrine pancreas, other mechanisms may be involved. We have shown that a potential&#xD;
      contributing factor to the patho-physiology of CFRD may be an abnormal gut derived hormonal&#xD;
      profile, specifically of lower incretin hormone responses, prior to development of CFRD.&#xD;
&#xD;
      We propose that an altered incretin response, probably due to impaired interaction of&#xD;
      nutrients with the gut mucosa due to thickened secretions, may play a role in the development&#xD;
      of the disease. Specifically, low GIP and GLP-1, may explain the poor β-cell function&#xD;
      observed in these patients prior to CFRD appearance. These incretins have known trophic&#xD;
      effects on β-cells, and thus their lower levels may contribute to the development of&#xD;
      quantitative as well as qualitative defects in β-cell function and thus may lead to the&#xD;
      development of CFRD. Thus, increasing levels of these incretins using a DPP-IV inhibitor may&#xD;
      improve glucose metabolism and delay/prevent the development of CFRD.&#xD;
&#xD;
      We hypothesize that Saxagliptin will increase the oDI compared to placebo and will thus&#xD;
      provide relative protection from diabetes development and in addition we expect that&#xD;
      Saxagliptin will lead to overall increased insulin concentrations and thus shift the&#xD;
      metabolic milieu to a more anabolic state. This will manifest as weight gain and reduction in&#xD;
      inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The following proposal includes testing the utility of DPP-IV inhibition in adult patients&#xD;
      with CF without CFRD. This will be achieved by a randomized double blind controlled trial of&#xD;
      Saxagliptin 5 mg vs. placebo which will be performed for 3 months in 60 patients with CF&#xD;
      without CFRD. The study will be for 3 months of use and will consist of two arms:&#xD;
&#xD;
        1. Saxagliptin 5mg&#xD;
&#xD;
        2. Placebo. the primary outcome of this study will be the oral disposition index oDI ,&#xD;
           derived from the OGTT. The oDI has been shown across age groups and metabolic phenotypes&#xD;
           to be an excellent predictor of diabetes development over time . We postulate that&#xD;
           Saxagliptin will increase incretin concentrations and thus improve insulin secretion.&#xD;
           This will manifest as an increased oral disposition index (oDI), reflecting an improved&#xD;
           beta cell response in the context of prevailing insulin sensitivity. The oDI is a useful&#xD;
           predictor of diabetes development over time and its increase will provide evidence for&#xD;
           protection from diabetes in this special study population&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>June 2015</start_date>
  <completion_date type="Anticipated">June 2016</completion_date>
  <primary_completion_date type="Anticipated">June 2016</primary_completion_date>
  <phase>N/A</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>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Oral Disposition Index</measure>
    <time_frame>The ODI will be calculated at baseline (Day 1) and at End point (day 90- 3 months)</time_frame>
    <description>The oDI is a useful predictor of diabetes development over time and its increase will provide evidence for protection from diabetes in this special study population</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo intake during 3 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saxagliptin 5mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Saxagliptin dose of 5mg for 3 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saxagliptin</intervention_name>
    <arm_group_label>Saxagliptin 5mg</arm_group_label>
    <other_name>Onglyza</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater than 18 years&#xD;
&#xD;
          -  Diagnosis of CF&#xD;
&#xD;
          -  No CFRD on baseline OGTT&#xD;
&#xD;
          -  Normal kidney function&#xD;
&#xD;
          -  No history of pancreatitis&#xD;
&#xD;
          -  Able and willing to consent and participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute illness/exacerbation of CF associated lung disease&#xD;
&#xD;
          -  Receiving immune-modulators following lung/pancreas transplant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eitan Kerem, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hadassah Ein Kerem</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ram Weiss, MD PhD</last_name>
    <phone>+972-50-894-6469</phone>
    <email>ramw@ekmd.huji.ac.il</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hadassah Ein Kerem/Har Hazofim</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
    <contact>
      <last_name>Ram Weiss, MD PhD</last_name>
      <email>ramw@ekmd.huji.ac.il</email>
    </contact>
    <investigator>
      <last_name>Eitan Kerem, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Limor Marko, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>April 15, 2015</last_update_submitted>
  <last_update_submitted_qc>April 15, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 16, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hadassah Medical Organization</investigator_affiliation>
    <investigator_full_name>Ram Weiss</investigator_full_name>
    <investigator_title>Head of the Department of Human Metabolism and Nutrition</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Saxagliptin</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/NCT02239458
org study id: 0388-14-HMO
nct id: NCT02239458
lead sponsor: 
Cystic fibrosis related diabetes (CFRD) is a common co-morbidity in patients with CF. The
      underlying pathophysiology of cystic fibrosis related diabetes (CFRD) is still a matter of
      investigation. In addition to localized tissue damage developing similar to that of the
      exocrine pancreas, other mechanisms may be involved. We have shown that a potential
      contributing factor to the patho-physiology of CFRD may be an abnormal gut derived hormonal
      profile, specifically of lower incretin hormone responses, prior to development of CFRD.

      We propose that an altered incretin response, probably due to impaired interaction of
      nutrients with the gut mucosa due to thickened secretions, may play a role in the development
      of the disease. Specifically, low GIP and GLP-1, may explain the poor β-cell function
      observed in these patients prior to CFRD appearance. These incretins have known trophic
      effects on β-cells, and thus their lower levels may contribute to the development of
      quantitative as well as qualitative defects in β-cell function and thus may lead to the
      development of CFRD. Thus, increasing levels of these incretins using a DPP-IV inhibitor may
      improve glucose metabolism and delay/prevent the development of CFRD.

      We hypothesize that Saxagliptin will increase the oDI compared to placebo and will thus
      provide relative protection from diabetes development and in addition we expect that
      Saxagliptin will lead to overall increased insulin concentrations and thus shift the
      metabolic milieu to a more anabolic state. This will manifest as weight gain and reduction in
      inflammation.
The following proposal includes testing the utility of DPP-IV inhibition in adult patients
      with CF without CFRD. This will be achieved by a randomized double blind controlled trial of
      Saxagliptin 5 mg vs. placebo which will be performed for 3 months in 60 patients with CF
      without CFRD. The study will be for 3 months of use and will consist of two arms:

        1. Saxagliptin 5mg

        2. Placebo. the primary outcome of this study will be the oral disposition index oDI ,
           derived from the OGTT. The oDI has been shown across age groups and metabolic phenotypes
           to be an excellent predictor of diabetes development over time . We postulate that
           Saxagliptin will increase incretin concentrations and thus improve insulin secretion.
           This will manifest as an increased oral disposition index (oDI), reflecting an improved
           beta cell response in the context of prevailing insulin sensitivity. The oDI is a useful
           predictor of diabetes development over time and its increase will provide evidence for
           protection from diabetes in this special study population
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Investigator)
measure: Oral Disposition Index
time frame: The ODI will be calculated at baseline (Day 1) and at End point (day 90- 3 months)
description: The oDI is a useful predictor of diabetes development over time and its increase will provide evidence for protection from diabetes in this special study population
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo intake during 3 months
arm group label: Saxagliptin 5mg
arm group type: Active Comparator
description: Saxagliptin dose of 5mg for 3 months
intervention type: Drug
intervention name: Saxagliptin
arm group label: Saxagliptin 5mg
other name: Onglyza
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Eitan Kerem, MD
role: Principal Investigator
affiliation: Hadassah Ein Kerem
last name: Ram Weiss, MD PhD
phone: +972-50-894-6469
email: ramw@ekmd.huji.ac.il
facility: 
contact: 
investigator: 
investigator: 
country: Israel
responsible party type: Sponsor-Investigator
investigator affiliation: Hadassah Medical Organization
investigator full name: Ram Weiss
investigator title: Head of the Department of Human Metabolism and Nutrition
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Saxagliptin