<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/NCT02225756</url>
  </required_header>
  <id_info>
    <org_study_id>P110119</org_study_id>
    <nct_id>NCT02225756</nct_id>
  </id_info>
  <brief_title>Cyclosporine A in Patients With Small Diameter Abdominal Aortic Aneurysms</brief_title>
  <acronym>ACA4</acronym>
  <official_title>Brief Administration of Cyclosporine A to Induce the Stabilisation of the Diameter of Small Diameter Abdominal Aortic Aneurysms.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aneurysms of the aorta are dilatations of the main artery in the body that distributes blood&#xD;
      to organs. Aneurysms expose patients to aortic rupture. The risk of aortic rupture is high&#xD;
      for large aneurysms, and low for small aneurysms. Currently, if the diameter of a small&#xD;
      aneurysm grows up to a level at risk for rupture, surgery is indicated to prevent rupture. A&#xD;
      drug that would stop growth of small aneurysms would obviate aortic surgery, the current&#xD;
      treatment to prevent aortic rupture in patients. The ACA4 study aims at testing the&#xD;
      possibility to stop growth of small aortic aneurysms in the abdomen with a drug, cyclosporine&#xD;
      A. Patients with small aneurysms will receive cyclosporine A orally, or a placebo (fake&#xD;
      liquid), every day during a short period of time. Efficacy of the drug will be evaluated by&#xD;
      measuring the diameter of the aneurysm during 2 years after treatment cessation. Drug safety&#xD;
      analysis will evaluate the impact of the drug on renal function, blood pressure, and other&#xD;
      parameters. In case of adverse event during the drug administration phase, dose of the drug&#xD;
      or of the placebo will be decreased or administration stopped.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Abdominal aortic aneurysms (AAAs) expose patients to death caused by aortic rupture. Although&#xD;
      screening of AAAs has been shown to decrease AAA-related mortality, translation into medical&#xD;
      practice of screening is limited because there is no specific treatment to limit growth of&#xD;
      AAAs below diameter thresholds for open surgery or stent graft. We have developed different&#xD;
      approaches aimed at inducing healing and thereby stabilizing formed AAAs in animal models. We&#xD;
      have identified TGF-beat1 as an inducer of experimental AAA healing. Cyclosporine A is an&#xD;
      inducer of tumor growth factor - beta1 (TGF-beta1) in experimental AAAs and in human&#xD;
      atherosclerotic AAAs in vitro, causing overgrowth of inflamed tissues. Since AAAs are caused&#xD;
      by aortic wall atrophy, we have hypothesised and confirmed in animals, that cyclosporine AAA,&#xD;
      when administrated during a short period of time, durably stabilizes small AAA diameter in&#xD;
      animals, while inducing aortic wall reconstruction and healing.&#xD;
&#xD;
      The clinical trial ACA4 is a multicentric randomized, placebo controlled, double blind trial&#xD;
      that will enrol 360 patients with small AAAs in France. Two doses of cyclosporine A will be&#xD;
      tested against a placebo (three arms). Drug administration will be short, and AAA diameter&#xD;
      evaluation will be performed for 2 years, by CT-scanner (main outcome) with no contrast, and&#xD;
      duplex-scanner.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2013</start_date>
  <completion_date type="Anticipated">September 2018</completion_date>
  <primary_completion_date type="Anticipated">September 2017</primary_completion_date>
  <phase>Phase 2</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>AAA diameter evolution on CT-scanner 12 months after treatment interruption</measure>
    <time_frame>1 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AAA diameter evolution on duplex-scanner 12 months after treatment interruption</measure>
    <time_frame>1 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal function (creatinine clearance)</measure>
    <time_frame>at inclusion visit, V4 and V8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All cause cardiovascular mortality and morbidity</measure>
    <time_frame>at V1 and V8</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">360</enrollment>
  <condition>Abdominal Aortic Aneurysm,</condition>
  <condition>Small Abdominal Aortic Aneurysm</condition>
  <arm_group>
    <arm_group_label>Cyclosporine A dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cyclosporine A dose 2</arm_group_label>
    <arm_group_type>Experimental</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>Cyclosporine A</intervention_name>
    <description>Oral administration for a short time of cyclosporine A dose 1</description>
    <arm_group_label>Cyclosporine A dose 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclosporine A</intervention_name>
    <description>Oral administration for a short time of cyclosporine A dose 2</description>
    <arm_group_label>Cyclosporine A dose 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral administration for a short time of placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male patients with asymptomatic AAA ≥ 30 mm, ≤ 49 mm&#xD;
&#xD;
          -  Female patients with asymptomatic AAA ≥ 25 mm, ≤ 44 mm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Common iliac aneurysm &gt; 25 mm&#xD;
&#xD;
          -  Saccular aneurysm of the aorta&#xD;
&#xD;
          -  Inflammatory aneurysm&#xD;
&#xD;
          -  No signature of informed consent&#xD;
&#xD;
          -  Renal dysfunction&#xD;
&#xD;
          -  Diabetes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eric Allaire, MD. PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Eric Allaire, MD. PhD.</last_name>
    <phone>(0)1 49 81 44 20</phone>
    <phone_ext>+33</phone_ext>
    <email>eric.allaire@hmn.aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Morgane Quéré-Carne, CRA</last_name>
    <phone>(0)1 49 81 37 52</phone>
    <phone_ext>+33</phone_ext>
    <email>morgane.quere-carne@hmn.aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Henri Mondor Hospital</name>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marie-Antoinette Sevestre, MD, PhD</last_name>
      <phone>(0)3 22 45 56 24</phone>
      <phone_ext>+33</phone_ext>
      <email>sevestre.marie-antoinette@chu-amiens.fr</email>
    </contact>
    <contact_backup>
      <last_name>Patrick Lermusiaux, MD, PhD</last_name>
      <phone>(0)4 72 11 76 76</phone>
      <phone_ext>+33</phone_ext>
      <email>patrick.lermusiaux@chu-lyon.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Eric Allaire, MD. PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>June 1, 2015</last_update_submitted>
  <last_update_submitted_qc>June 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug therapy</keyword>
  <keyword>Prevention and control</keyword>
  <keyword>Healing</keyword>
  <keyword>Tissue regeneration</keyword>
  <keyword>Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm, Abdominal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclosporine</mesh_term>
    <mesh_term>Cyclosporins</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/NCT02225756
org study id: P110119
nct id: NCT02225756
lead sponsor: 
has dmc: Yes
Aneurysms of the aorta are dilatations of the main artery in the body that distributes blood
      to organs. Aneurysms expose patients to aortic rupture. The risk of aortic rupture is high
      for large aneurysms, and low for small aneurysms. Currently, if the diameter of a small
      aneurysm grows up to a level at risk for rupture, surgery is indicated to prevent rupture. A
      drug that would stop growth of small aneurysms would obviate aortic surgery, the current
      treatment to prevent aortic rupture in patients. The ACA4 study aims at testing the
      possibility to stop growth of small aortic aneurysms in the abdomen with a drug, cyclosporine
      A. Patients with small aneurysms will receive cyclosporine A orally, or a placebo (fake
      liquid), every day during a short period of time. Efficacy of the drug will be evaluated by
      measuring the diameter of the aneurysm during 2 years after treatment cessation. Drug safety
      analysis will evaluate the impact of the drug on renal function, blood pressure, and other
      parameters. In case of adverse event during the drug administration phase, dose of the drug
      or of the placebo will be decreased or administration stopped.
Abdominal aortic aneurysms (AAAs) expose patients to death caused by aortic rupture. Although
      screening of AAAs has been shown to decrease AAA-related mortality, translation into medical
      practice of screening is limited because there is no specific treatment to limit growth of
      AAAs below diameter thresholds for open surgery or stent graft. We have developed different
      approaches aimed at inducing healing and thereby stabilizing formed AAAs in animal models. We
      have identified TGF-beat1 as an inducer of experimental AAA healing. Cyclosporine A is an
      inducer of tumor growth factor - beta1 (TGF-beta1) in experimental AAAs and in human
      atherosclerotic AAAs in vitro, causing overgrowth of inflamed tissues. Since AAAs are caused
      by aortic wall atrophy, we have hypothesised and confirmed in animals, that cyclosporine AAA,
      when administrated during a short period of time, durably stabilizes small AAA diameter in
      animals, while inducing aortic wall reconstruction and healing.

      The clinical trial ACA4 is a multicentric randomized, placebo controlled, double blind trial
      that will enrol 360 patients with small AAAs in France. Two doses of cyclosporine A will be
      tested against a placebo (three arms). Drug administration will be short, and AAA diameter
      evaluation will be performed for 2 years, by CT-scanner (main outcome) with no contrast, and
      duplex-scanner.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: AAA diameter evolution on CT-scanner 12 months after treatment interruption
time frame: 1 years
measure: AAA diameter evolution on duplex-scanner 12 months after treatment interruption
time frame: 1 years
measure: Renal function (creatinine clearance)
time frame: at inclusion visit, V4 and V8
measure: All cause cardiovascular mortality and morbidity
time frame: at V1 and V8
arm group label: Cyclosporine A dose 1
arm group type: Experimental
arm group label: Cyclosporine A dose 2
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Cyclosporine A
description: Oral administration for a short time of cyclosporine A dose 1
arm group label: Cyclosporine A dose 1
intervention type: Drug
intervention name: Cyclosporine A
description: Oral administration for a short time of cyclosporine A dose 2
arm group label: Cyclosporine A dose 2
intervention type: Drug
intervention name: Placebo
description: Oral administration for a short time of placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: No
last name: Eric Allaire, MD. PhD.
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Eric Allaire, MD. PhD.
phone: (0)1 49 81 44 20
phone ext: +33
email: eric.allaire@hmn.aphp.fr
last name: Morgane Quéré-Carne, CRA
phone: (0)1 49 81 37 52
phone ext: +33
email: morgane.quere-carne@hmn.aphp.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Aneurysm
mesh term: Aortic Aneurysm
mesh term: Aortic Aneurysm, Abdominal
mesh term: Cyclosporine
mesh term: Cyclosporins