<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/NCT04500665</url>
  </required_header>
  <id_info>
    <org_study_id>2020P002468</org_study_id>
    <secondary_id>K23HL150311</secondary_id>
    <nct_id>NCT04500665</nct_id>
  </id_info>
  <brief_title>Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine</brief_title>
  <official_title>Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to determine the efficacy and safety of colchicine in patients with&#xD;
      chronic kidney disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 1, 2021</start_date>
  <completion_date type="Anticipated">November 11, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Between-group change in left ventricular global longitudinal strain</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assessed using transthoracic echocardiography</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Between-group change in left ventricular systolic and diastolic function</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assessed using transthoracic echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Between-group change in left ventricular volumes</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assessed using transthoracic echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Between-group change in left ventricular size</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assessed using transthoracic echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Between-group change in systemic inflammation</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assessed using C-reactive protein</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Chronic Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>Colchicine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Colchicine 0.3 mg once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colchicine</intervention_name>
    <description>Colchicine</description>
    <arm_group_label>Colchicine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        A. Inclusion Criteria:&#xD;
&#xD;
          1. Age 21 years to 80 years&#xD;
&#xD;
          2. eGFR of 15 to 75 mL/min per 1.73 m2&#xD;
&#xD;
          3. Urine albumin-to-creatinine ratio of 200 mg/g or greater&#xD;
&#xD;
          4. Serum high-sensitivity C-reactive protein concentration of greater than 2 mg/L within&#xD;
             2 weeks of screening&#xD;
&#xD;
          5. Reduction in high-sensitivity C-reactive protein concentration of 25% or greater&#xD;
             during the open-label run-in phase&#xD;
&#xD;
          6. Left ventricular global longitudinal strain of -16% or worse within the past 12 months&#xD;
&#xD;
          7. Use of maximally tolerated doses of an angiotensin-converting enzyme inhibitor or&#xD;
             angiotensin receptor blocker if urine albumin-to-creatinine ratio greater than 300&#xD;
             mg-g&#xD;
&#xD;
          8. Use of a sodium-glucose co-transporter-2 inhibitor if indicated in the opinion of the&#xD;
             participant's primary clinician&#xD;
&#xD;
          9. Willing and able to provide written informed consent and to adhere to the study&#xD;
             protocol&#xD;
&#xD;
        B. Exclusion Criteria:&#xD;
&#xD;
          1. History of intolerance or allergy to colchicine&#xD;
&#xD;
          2. Hospitalization for any reason within the previous 30 days&#xD;
&#xD;
          3. Acute condition that requires emergent treatment in the opinion of a physician&#xD;
             investigator&#xD;
&#xD;
          4. Stage C or D heart failure according to ACC-AHA criteria77&#xD;
&#xD;
          5. Left ventricular ejection fraction less than 40%&#xD;
&#xD;
          6. Prior acute coronary syndrome&#xD;
&#xD;
          7. Symptomatic valvular heart disease&#xD;
&#xD;
          8. Congenital heart disease (corrected or uncorrected)&#xD;
&#xD;
          9. History of orthotopic heart transplant&#xD;
&#xD;
         10. Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater&#xD;
             than 90 mm Hg&#xD;
&#xD;
         11. Kidney failure, defined as kidney transplant recipient or requirement for hemodialysis&#xD;
             or peritoneal dialysis&#xD;
&#xD;
         12. Worsening kidney function or acute kidney injury, defined as an increase in serum&#xD;
             creatinine of greater than 0.3 mg/dL in the previous 30 days or 50% within the&#xD;
             previous 7 days&#xD;
&#xD;
         13. Use of immunosuppressive or anti-inflammatory medications within the previous 30 days,&#xD;
             with the exception of less than 5 days of non-steroidal anti-inflammatory drugs or&#xD;
             corticosteroids for acute pain or other acute conditions that have since fully&#xD;
             resolved provided that the last dose of non-steroid anti-inflammatory drug was at&#xD;
             least 7 days before enrollment&#xD;
&#xD;
         14. Diagnosis of rheumatoid arthritis, systemic lupus erythematosus, other systemic&#xD;
             auto-immune or auto-inflammatory condition&#xD;
&#xD;
         15. Familial Mediterranean Fever, gout (unless no flare within the previous 12 months),&#xD;
             pericarditis or other indications for colchicine treatment&#xD;
&#xD;
         16. Use of systemic antimicrobial therapy within the previous 30 days or active infection&#xD;
&#xD;
         17. History of respiratory illness that, in the opinion of a physician investigator, may&#xD;
             increase the risk of pneumonia&#xD;
&#xD;
         18. Surgery within the previous 30 days or surgery planned to occur within the expected&#xD;
             study period&#xD;
&#xD;
         19. Current malignancy or receipt of treatment for malignancy within the previous 1 year&#xD;
&#xD;
         20. Frailty or life-expectancy shortened by comorbidity such as cancer that would increase&#xD;
             the participant's risk in the opinion of a physician investigator&#xD;
&#xD;
         21. Neutrophil count &lt; 2,000 cells/mm3&#xD;
&#xD;
         22. Platelet count &lt; 50,000 cells/mm3&#xD;
&#xD;
         23. Concomitant use of a P-gp inhibitor (e.g., cyclosporine, ranolazine, digoxin) and/or&#xD;
             moderate-strong CYP3A4 inhibitor (e.g., clarithromycin, indinavir, itraconazole,&#xD;
             ritonavir, nefazodone, diltiazem, verapamil, grapefruit juice, fluconazole)&#xD;
&#xD;
         24. Medications that may cause myopathy or rhabdomyolysis (i.e., simvastatin, gemfibrozil,&#xD;
             fenofibrate) , a creatine kinase level after the run-in period that exceeds the upper&#xD;
             limit of the normal laboratory reference range (if baseline was below the upper limit)&#xD;
             or that increases by 50% or more from pre- to post-run-in&#xD;
&#xD;
         25. Moderate-severe hepatic disease (Child-Pugh B or C)&#xD;
&#xD;
         26. Pregnant or unwilling/unable to assure appropriate contraception&#xD;
&#xD;
         27. Breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leo F Buckley, Pharm.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Leo F Buckley, Pharm.D.</last_name>
    <phone>617-732-5500</phone>
    <email>lfbuckley@bwh.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Leo Buckley, PharmD</last_name>
      <phone>617-732-4497</phone>
      <email>lfbuckley@bwh.harvard.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>July 27, 2023</last_update_submitted>
  <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Leo F. Buckley, PharmD</investigator_full_name>
    <investigator_title>Clinical Pharmacy Specialist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colchicine</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/NCT04500665
org study id: 2020P002468
secondary id: K23HL150311
nct id: NCT04500665
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study is designed to determine the efficacy and safety of colchicine in patients with
      chronic kidney disease.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Between-group change in left ventricular global longitudinal strain
time frame: 4 weeks
description: Assessed using transthoracic echocardiography
measure: Between-group change in left ventricular systolic and diastolic function
time frame: 4 weeks
description: Assessed using transthoracic echocardiography
measure: Between-group change in left ventricular volumes
time frame: 4 weeks
description: Assessed using transthoracic echocardiography
measure: Between-group change in left ventricular size
time frame: 4 weeks
description: Assessed using transthoracic echocardiography
measure: Between-group change in systemic inflammation
time frame: 4 weeks
description: Assessed using C-reactive protein
arm group label: Colchicine
arm group type: Experimental
description: Colchicine 0.3 mg once daily
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo once daily
intervention type: Drug
intervention name: Colchicine
description: Colchicine
arm group label: Colchicine
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: No
last name: Leo F Buckley, Pharm.D.
role: Principal Investigator
affiliation: Brigham and Women's Hospital
last name: Leo F Buckley, Pharm.D.
phone: 617-732-5500
email: lfbuckley@bwh.harvard.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Leo F. Buckley, PharmD
investigator title: Clinical Pharmacy Specialist
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Cardiomyopathies
mesh term: Colchicine
sharing ipd: No