<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/NCT02995512</url>
  </required_header>
  <id_info>
    <org_study_id>16-01704</org_study_id>
    <nct_id>NCT02995512</nct_id>
  </id_info>
  <brief_title>Mechanistic Effects of Colchicine in Patients With Myocardial Infarction</brief_title>
  <official_title>Mechanistic Effects of Colchicine in Patients With Myocardial Infarction A Single Center Phase 4 Single Arm Open-label Study Evaluating the FDA-approved Drug, Colchicine, at the FDA-approved Gout Dose in Patients With Myocardial Infarction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to determine the immuno-modulatory mechanistic effects of colchicine&#xD;
      in patients with myocardial infarction (MI). Investigators hypothesize that colchicine exerts&#xD;
      its anti-inflammatory properties by switching the metabolism of neutrophils, thereby reducing&#xD;
      the expression of adhesion molecules responsible for their recruitment in MI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot study to explore the mechanistic effects of colchicine in patients with MI.&#xD;
      The study will be conducted sequentially in 3 parts:&#xD;
&#xD;
        1. Blood will be collected from up to 10 healthy volunteers for protocol development.&#xD;
           (Group 1).&#xD;
&#xD;
        2. Blood will be collected from 20 MI patients within 24 hours of presentation at New York&#xD;
           University (NYU) Langone Medical Center and Bellevue Hospital Center (BHC). Neutrophil&#xD;
           adhesion to human aortic endothelial cells, quantitative expression of adhesion&#xD;
           molecules on the surface of neutrophils, quantitative levels of adhesion molecules on&#xD;
           neutrophils and endothelial cells, and neutrophil metabolism, using a Seahorse Analyzer&#xD;
           will be evaluated pre- and post-addition of in vitro colchicine. (Group 2)&#xD;
&#xD;
        3. The standard low-dose loading regimen of colchicine (1.2 mg followed by 0.6 mg one hour&#xD;
           later) will be administered to 20 patients with MI at BHC. Blood will be collected prior&#xD;
           to drug administration, 2 to 3 hours after completion of the colchicine load, and 23 to&#xD;
           24 hours after the completion of the colchicine load. Neutrophil adhesion to human&#xD;
           aortic endothelial cells, quantitative expression of adhesion molecules on the surface&#xD;
           of neutrophils, quantitative levels of adhesion molecules on neutrophils and endothelial&#xD;
           cells, and neutrophil metabolism will be evaluated pre- and post-addition of in vitro&#xD;
           colchicine (exact markers will be determined based on the results of in viro studies&#xD;
           above). (Group 3)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    feasibility&#xD;
  </why_stopped>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Actual">September 12, 2018</completion_date>
  <primary_completion_date type="Actual">September 12, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of neutrophils adherent to TNFα-stimulated endothelial cells</measure>
    <time_frame>1 Day</time_frame>
    <description>Metabolism of neutrophils will be measured using the Seahorse assay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Levels of adhesion molecules on neutrophils and endothelial cells quantified using PCR</measure>
    <time_frame>1 Day</time_frame>
    <description>Metabolism of neutrophils will be measured using the Seahorse assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of adhesion molecules on the surface of neutrophils assessed via flow cytometry</measure>
    <time_frame>1 Day</time_frame>
    <description>Measurements of L-selectin, CD11b, and active CD11b will be made via an Accuri C6 flow cytometer using standard antibodies on an aliquot of whole blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measures of neutrophil metabolism (e.g. O2 consumption)</measure>
    <time_frame>1 Day</time_frame>
    <description>Metabolism of neutrophils will be measured using the Seahorse assay.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Myocardial Infarction (MI) Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colchicine 0.6 mg tablets</intervention_name>
    <description>1.2 mg PO followed by 0.6 mg PO 1 hour later</description>
    <arm_group_label>Myocardial Infarction (MI) Patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age for the healthy volunteer subset.&#xD;
&#xD;
          -  18 years of age and within 24 hours of an MI for the MI subset.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects in all 3 groups will be excluded if they meet one of the following criteria&#xD;
&#xD;
          -  history of myelodysplasia;&#xD;
&#xD;
          -  Use of anti-inflammatory medications, with the exception of aspirin, within 5&#xD;
             half-lives;&#xD;
&#xD;
          -  medications known to interact with colchicine;&#xD;
&#xD;
          -  known creatinine clearance &lt;30 cc/minute (severe kidney disease);&#xD;
&#xD;
          -  pregnant; or&#xD;
&#xD;
          -  Unable to consent.&#xD;
&#xD;
        MI subjects who will have oral colchicine administered will have the following additional&#xD;
        exclusion criteria:&#xD;
&#xD;
          -  history of intolerance to colchicine;&#xD;
&#xD;
          -  acute or chronic symptoms of diarrhea within 72 hours prior to enrollment;&#xD;
&#xD;
          -  hemoglobin &lt;10 g/dL or clinical evidence of active bleeding during the study period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Binita Shah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <last_update_submitted>April 16, 2019</last_update_submitted>
  <last_update_submitted_qc>April 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>myocardial infarction</keyword>
  <keyword>colchicine</keyword>
  <keyword>anti-inflammatory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colchicine</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/NCT02995512
org study id: 16-01704
nct id: NCT02995512
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The aim of this study is to determine the immuno-modulatory mechanistic effects of colchicine
      in patients with myocardial infarction (MI). Investigators hypothesize that colchicine exerts
      its anti-inflammatory properties by switching the metabolism of neutrophils, thereby reducing
      the expression of adhesion molecules responsible for their recruitment in MI.
This is a pilot study to explore the mechanistic effects of colchicine in patients with MI.
      The study will be conducted sequentially in 3 parts:

        1. Blood will be collected from up to 10 healthy volunteers for protocol development.
           (Group 1).

        2. Blood will be collected from 20 MI patients within 24 hours of presentation at New York
           University (NYU) Langone Medical Center and Bellevue Hospital Center (BHC). Neutrophil
           adhesion to human aortic endothelial cells, quantitative expression of adhesion
           molecules on the surface of neutrophils, quantitative levels of adhesion molecules on
           neutrophils and endothelial cells, and neutrophil metabolism, using a Seahorse Analyzer
           will be evaluated pre- and post-addition of in vitro colchicine. (Group 2)

        3. The standard low-dose loading regimen of colchicine (1.2 mg followed by 0.6 mg one hour
           later) will be administered to 20 patients with MI at BHC. Blood will be collected prior
           to drug administration, 2 to 3 hours after completion of the colchicine load, and 23 to
           24 hours after the completion of the colchicine load. Neutrophil adhesion to human
           aortic endothelial cells, quantitative expression of adhesion molecules on the surface
           of neutrophils, quantitative levels of adhesion molecules on neutrophils and endothelial
           cells, and neutrophil metabolism will be evaluated pre- and post-addition of in vitro
           colchicine (exact markers will be determined based on the results of in viro studies
           above). (Group 3)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of neutrophils adherent to TNFα-stimulated endothelial cells
time frame: 1 Day
description: Metabolism of neutrophils will be measured using the Seahorse assay.
measure: Levels of adhesion molecules on neutrophils and endothelial cells quantified using PCR
time frame: 1 Day
description: Metabolism of neutrophils will be measured using the Seahorse assay.
measure: Expression of adhesion molecules on the surface of neutrophils assessed via flow cytometry
time frame: 1 Day
description: Measurements of L-selectin, CD11b, and active CD11b will be made via an Accuri C6 flow cytometer using standard antibodies on an aliquot of whole blood.
measure: Measures of neutrophil metabolism (e.g. O2 consumption)
time frame: 1 Day
description: Metabolism of neutrophils will be measured using the Seahorse assay.
arm group label: Myocardial Infarction (MI) Patients
arm group type: Experimental
intervention type: Drug
intervention name: Colchicine 0.6 mg tablets
description: 1.2 mg PO followed by 0.6 mg PO 1 hour later
arm group label: Myocardial Infarction (MI) Patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Binita Shah, MD
role: Principal Investigator
affiliation: NYU Langone Health
country: United States
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: Infarction
mesh term: Colchicine