<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/NCT03271580</url>
  </required_header>
  <id_info>
    <org_study_id>1808802536</org_study_id>
    <nct_id>NCT03271580</nct_id>
  </id_info>
  <brief_title>Biofilm Modified Macrophage Phenotype and Function in Diabetic Wound Healing</brief_title>
  <official_title>Biofilm Modified Macrophage Phenotype and Function in Diabetic Wound Healing</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to learn more about biofilm and to see how it affects diabetic&#xD;
      wounds. A biofilm can occur if a chronic infection causes bacteria to grow in a slime&#xD;
      enclosed group. This grouping of bacteria is called a biofilm.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is one study visit with a 14-week follow-up that will take place during the&#xD;
      participants standard of care visit at the Indiana University Health Comprehensive Wound&#xD;
      Center (CWC). The following procedures will take place once your appointment has been&#xD;
      completed:&#xD;
&#xD;
        -  Informed consent will be signed (if not previously signed)&#xD;
&#xD;
        -  A hemoglobin A1c drawn will be taken by research personnel, if one has not been done&#xD;
           within the last 90 days to check your average blood sugar level.&#xD;
&#xD;
        -  An Ankle Brachial Index (ABI) will be obtained if the participant has a leg wound. This&#xD;
           is to ensure that participants have adequate blood flow to your wound. This is a&#xD;
           non-invasive test which measures blood pressure in both of the participants arms and&#xD;
           ankles.&#xD;
&#xD;
        -  Demographics (such as your name and address and phone number, age), medical history,&#xD;
           current medications, current standard of care labs, and wound data (measurements, cause&#xD;
           of the wound, wound culture, assessments, treatments, and duration) will be recorded.&#xD;
           The participant's medical record number will also be recorded.&#xD;
&#xD;
        -  A photo of the wound site will be taken.&#xD;
&#xD;
        -  Wound Vac Collection - The wound vac sponge will be collected (waste by product of the&#xD;
           therapy) by the research staff.&#xD;
&#xD;
        -  An optional two 3 mm punch tissue biopsies will be obtained from the participant's&#xD;
           provider. To perform the biopsy, the area surrounding the wound will first be numbed&#xD;
           using a local anesthetic agent that will be injected at the wound site. Then, a&#xD;
           pencil-like instrument will be used to remove a small, thin cylinder of tissue. Each&#xD;
           biopsy is about the size of this dot. After the tissue is removed, a sterile gauze will&#xD;
           be placed on the area to stop any minor bleeding that may occur. The biopsies will be&#xD;
           looked at in the laboratory to look at the microorganisms. You will not receive the&#xD;
           results of the completed laboratory analysis. (Note: If two biopsies cannot be obtained&#xD;
           per your physician's discretion, only one biopsy, debridement tissue (dead tissue that&#xD;
           is removed from your wound) or no tissue will be obtained, and/or culture swabs (your&#xD;
           wound will be swabbed with something like a Q-tip to collect cells to test for bacteria&#xD;
           or other organisms in the wound) will be collected to test for infection.)&#xD;
&#xD;
      During the 14-week follow-up visit, research staff will review the participant's medical&#xD;
      chart to determine the final status of the wound. If the participant does not return to the&#xD;
      CWC at 14 weeks, the last CWC visit will be documented as the wound check follow-up. This&#xD;
      does not require the participant to return for an extra study visit. This information will&#xD;
      only be collected from their medical chart if available:&#xD;
&#xD;
        -  Final status of the wound (healing, not healing, healed)&#xD;
&#xD;
        -  Wound data (measurements), treatments, and any standard of care labs will be obtained&#xD;
&#xD;
        -  A photo of your wound from the medical chart will be obtained (if available)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 1, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Biofilm infection</measure>
    <time_frame>14 Weeks</time_frame>
    <description>Biofilm Infection using SEM and RT PCR analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>macrophage phenotyping</measure>
    <time_frame>14 Weeks</time_frame>
    <description>Wound macrophage phenotypes using flowcytometry, RTPCR and RNA Seq</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">28</enrollment>
  <condition>Wound</condition>
  <condition>Bacterial Infections</condition>
  <condition>Diabetes Mellitus</condition>
  <condition>Infected Ulcer of Skin</condition>
  <arm_group>
    <arm_group_label>Diabetic patients infected ulcers</arm_group_label>
    <description>Diabetic patients with HbA1c&lt;9 with who have wound 4weeks or longer with infection with following interventions:&#xD;
Finger prick test for HbA1c measurement&#xD;
Punch biopsy&#xD;
VAC sponge collection&#xD;
Ankle brachial index</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic patients non infected Ulcers</arm_group_label>
    <description>Diabetic patients with HbA1c&lt;9 who have wound 4 weeks or longer without infection with following interventions:&#xD;
Finger prick test for HbA1c measurement&#xD;
Punch biopsy&#xD;
VAC sponge collection&#xD;
Ankle brachial index</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Finger prick test for HbA1c measurement</intervention_name>
    <description>HbA1c measurement with finger prick method</description>
    <arm_group_label>Diabetic patients infected ulcers</arm_group_label>
    <arm_group_label>Diabetic patients non infected Ulcers</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Punch Biopsy</intervention_name>
    <description>Wound site will be anaesthetized, by punch biopsy tissue will be collected, wound site will be monitored for bleeding(if bleeding Cautery will be used to stop bleeding).</description>
    <arm_group_label>Diabetic patients infected ulcers</arm_group_label>
    <arm_group_label>Diabetic patients non infected Ulcers</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Vac Sponge Collection</intervention_name>
    <description>NPWT sponge which is discarded as biological waste, will be collected for wound macrophage isolation</description>
    <arm_group_label>Diabetic patients infected ulcers</arm_group_label>
    <arm_group_label>Diabetic patients non infected Ulcers</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ankle Brachial Index</intervention_name>
    <description>Blood pressure test</description>
    <arm_group_label>Diabetic patients infected ulcers</arm_group_label>
    <arm_group_label>Diabetic patients non infected Ulcers</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood, Wound Vac Sponge, Wound Tissue biopsy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Twenty-eight diabetic subjects with chronic foot ulcer(s) that are receiving Negative Wound&#xD;
        Pressure Therapy (NPWT) will be enrolled. Eighteen subjects will be infected and 10&#xD;
        subjects will be non-infected serving as the control for the study. The inclusion and&#xD;
        exclusion criteria were carefully selected to enroll diabetic patients who have wound&#xD;
        tissue oxygenation adequate to support wound healing.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 and above years old&#xD;
&#xD;
          2. Willing and able to provide informed consent&#xD;
&#xD;
          3. Willing and able to comply with protocol instructions, including biopsies and study&#xD;
             visits&#xD;
&#xD;
          4. Diabetics with an open wound&#xD;
&#xD;
          5. Receiving Negative Wound Pressure Therapy (NPWT)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inadequate arterial supply, as evidenced by any of the following (for wounds below the&#xD;
             knee):&#xD;
&#xD;
               1. TcOM &lt; 30mmHg&#xD;
&#xD;
               2. ABI &lt; 0.7&#xD;
&#xD;
               3. TBI &lt; 0.6&#xD;
&#xD;
          2. Women who are pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sashwati Roy, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bryce Hockman, CCRP</last_name>
    <phone>317 278 2715</phone>
    <email>bbhockma@iu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kaitlyn Depinet, FNP-C</last_name>
    <phone>317 278 2747</phone>
    <email>kdepinet@iu.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>IU Health Methodist Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bryce Hockman, CCRP</last_name>
      <phone>317-278-2715</phone>
      <email>bbhockma@iu.edu</email>
    </contact>
    <contact_backup>
      <last_name>Kaitlyn Depinet, FNP-C</last_name>
      <phone>317 278 2747</phone>
      <email>kdepinet@iu.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sashwati Roy, Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Breen JD, Karchmer AW. Staphylococcus aureus infections in diabetic patients. Infect Dis Clin North Am. 1995 Mar;9(1):11-24.</citation>
    <PMID>7769212</PMID>
  </reference>
  <reference>
    <citation>Davis SC, Martinez L, Kirsner R. The diabetic foot: the importance of biofilms and wound bed preparation. Curr Diab Rep. 2006 Dec;6(6):439-45. doi: 10.1007/s11892-006-0076-x.</citation>
    <PMID>17118226</PMID>
  </reference>
  <reference>
    <citation>James GA, Swogger E, Wolcott R, Pulcini Ed, Secor P, Sestrich J, Costerton JW, Stewart PS. Biofilms in chronic wounds. Wound Repair Regen. 2008 Jan-Feb;16(1):37-44. doi: 10.1111/j.1524-475X.2007.00321.x. Epub 2007 Dec 13.</citation>
    <PMID>18086294</PMID>
  </reference>
  <reference>
    <citation>Hanke ML, Angle A, Kielian T. MyD88-dependent signaling influences fibrosis and alternative macrophage activation during Staphylococcus aureus biofilm infection. PLoS One. 2012;7(8):e42476. doi: 10.1371/journal.pone.0042476. Epub 2012 Aug 3.</citation>
    <PMID>22879997</PMID>
  </reference>
  <reference>
    <citation>Hanke ML, Heim CE, Angle A, Sanderson SD, Kielian T. Targeting macrophage activation for the prevention and treatment of Staphylococcus aureus biofilm infections. J Immunol. 2013 Mar 1;190(5):2159-68. doi: 10.4049/jimmunol.1202348. Epub 2013 Jan 30. Erratum In: J Immunol. 2013 Jun 15;190(12):6709-10.</citation>
    <PMID>23365077</PMID>
  </reference>
  <reference>
    <citation>Neut D, Tijdens-Creusen EJ, Bulstra SK, van der Mei HC, Busscher HJ. Biofilms in chronic diabetic foot ulcers--a study of 2 cases. Acta Orthop. 2011 Jun;82(3):383-5. doi: 10.3109/17453674.2011.581265. Epub 2011 May 11. No abstract available.</citation>
    <PMID>21561305</PMID>
  </reference>
  <reference>
    <citation>Zhao G, Usui ML, Lippman SI, James GA, Stewart PS, Fleckman P, Olerud JE. Biofilms and Inflammation in Chronic Wounds. Adv Wound Care (New Rochelle). 2013 Sep;2(7):389-399. doi: 10.1089/wound.2012.0381.</citation>
    <PMID>24527355</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>March 24, 2023</last_update_submitted>
  <last_update_submitted_qc>March 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Sashwati Roy</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Wound healing</keyword>
  <keyword>Diabetes</keyword>
  <keyword>Inflammatory cells</keyword>
  <keyword>Macrophage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bacterial Infections</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_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/NCT03271580
org study id: 1808802536
nct id: NCT03271580
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to learn more about biofilm and to see how it affects diabetic
      wounds. A biofilm can occur if a chronic infection causes bacteria to grow in a slime
      enclosed group. This grouping of bacteria is called a biofilm.
There is one study visit with a 14-week follow-up that will take place during the
      participants standard of care visit at the Indiana University Health Comprehensive Wound
      Center (CWC). The following procedures will take place once your appointment has been
      completed:

        -  Informed consent will be signed (if not previously signed)

        -  A hemoglobin A1c drawn will be taken by research personnel, if one has not been done
           within the last 90 days to check your average blood sugar level.

        -  An Ankle Brachial Index (ABI) will be obtained if the participant has a leg wound. This
           is to ensure that participants have adequate blood flow to your wound. This is a
           non-invasive test which measures blood pressure in both of the participants arms and
           ankles.

        -  Demographics (such as your name and address and phone number, age), medical history,
           current medications, current standard of care labs, and wound data (measurements, cause
           of the wound, wound culture, assessments, treatments, and duration) will be recorded.
           The participant's medical record number will also be recorded.

        -  A photo of the wound site will be taken.

        -  Wound Vac Collection - The wound vac sponge will be collected (waste by product of the
           therapy) by the research staff.

        -  An optional two 3 mm punch tissue biopsies will be obtained from the participant's
           provider. To perform the biopsy, the area surrounding the wound will first be numbed
           using a local anesthetic agent that will be injected at the wound site. Then, a
           pencil-like instrument will be used to remove a small, thin cylinder of tissue. Each
           biopsy is about the size of this dot. After the tissue is removed, a sterile gauze will
           be placed on the area to stop any minor bleeding that may occur. The biopsies will be
           looked at in the laboratory to look at the microorganisms. You will not receive the
           results of the completed laboratory analysis. (Note: If two biopsies cannot be obtained
           per your physician's discretion, only one biopsy, debridement tissue (dead tissue that
           is removed from your wound) or no tissue will be obtained, and/or culture swabs (your
           wound will be swabbed with something like a Q-tip to collect cells to test for bacteria
           or other organisms in the wound) will be collected to test for infection.)

      During the 14-week follow-up visit, research staff will review the participant's medical
      chart to determine the final status of the wound. If the participant does not return to the
      CWC at 14 weeks, the last CWC visit will be documented as the wound check follow-up. This
      does not require the participant to return for an extra study visit. This information will
      only be collected from their medical chart if available:

        -  Final status of the wound (healing, not healing, healed)

        -  Wound data (measurements), treatments, and any standard of care labs will be obtained

        -  A photo of your wound from the medical chart will be obtained (if available)
observational model: Cohort
time perspective: Prospective
measure: Biofilm infection
time frame: 14 Weeks
description: Biofilm Infection using SEM and RT PCR analysis
measure: macrophage phenotyping
time frame: 14 Weeks
description: Wound macrophage phenotypes using flowcytometry, RTPCR and RNA Seq
arm group label: Diabetic patients infected ulcers
description: Diabetic patients with HbA1c<9 with who have wound 4weeks or longer with infection with following interventions:
Finger prick test for HbA1c measurement
Punch biopsy
VAC sponge collection
Ankle brachial index
arm group label: Diabetic patients non infected Ulcers
description: Diabetic patients with HbA1c<9 who have wound 4 weeks or longer without infection with following interventions:
Finger prick test for HbA1c measurement
Punch biopsy
VAC sponge collection
Ankle brachial index
intervention type: Diagnostic Test
intervention name: Finger prick test for HbA1c measurement
description: HbA1c measurement with finger prick method
arm group label: Diabetic patients infected ulcers
arm group label: Diabetic patients non infected Ulcers
intervention type: Procedure
intervention name: Punch Biopsy
description: Wound site will be anaesthetized, by punch biopsy tissue will be collected, wound site will be monitored for bleeding(if bleeding Cautery will be used to stop bleeding).
arm group label: Diabetic patients infected ulcers
arm group label: Diabetic patients non infected Ulcers
intervention type: Other
intervention name: Vac Sponge Collection
description: NPWT sponge which is discarded as biological waste, will be collected for wound macrophage isolation
arm group label: Diabetic patients infected ulcers
arm group label: Diabetic patients non infected Ulcers
intervention type: Other
intervention name: Ankle Brachial Index
description: Blood pressure test
arm group label: Diabetic patients infected ulcers
arm group label: Diabetic patients non infected Ulcers
Blood, Wound Vac Sponge, Wound Tissue biopsy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sashwati Roy, PhD
role: Principal Investigator
affiliation: Indiana University
last name: Bryce Hockman, CCRP
phone: 317 278 2715
email: bbhockma@iu.edu
last name: Kaitlyn Depinet, FNP-C
phone: 317 278 2747
email: kdepinet@iu.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
citation: Breen JD, Karchmer AW. Staphylococcus aureus infections in diabetic patients. Infect Dis Clin North Am. 1995 Mar;9(1):11-24.
PMID: 7769212
citation: Davis SC, Martinez L, Kirsner R. The diabetic foot: the importance of biofilms and wound bed preparation. Curr Diab Rep. 2006 Dec;6(6):439-45. doi: 10.1007/s11892-006-0076-x.
PMID: 17118226
citation: James GA, Swogger E, Wolcott R, Pulcini Ed, Secor P, Sestrich J, Costerton JW, Stewart PS. Biofilms in chronic wounds. Wound Repair Regen. 2008 Jan-Feb;16(1):37-44. doi: 10.1111/j.1524-475X.2007.00321.x. Epub 2007 Dec 13.
PMID: 18086294
citation: Hanke ML, Angle A, Kielian T. MyD88-dependent signaling influences fibrosis and alternative macrophage activation during Staphylococcus aureus biofilm infection. PLoS One. 2012;7(8):e42476. doi: 10.1371/journal.pone.0042476. Epub 2012 Aug 3.
PMID: 22879997
citation: Hanke ML, Heim CE, Angle A, Sanderson SD, Kielian T. Targeting macrophage activation for the prevention and treatment of Staphylococcus aureus biofilm infections. J Immunol. 2013 Mar 1;190(5):2159-68. doi: 10.4049/jimmunol.1202348. Epub 2013 Jan 30. Erratum In: J Immunol. 2013 Jun 15;190(12):6709-10.
PMID: 23365077
citation: Neut D, Tijdens-Creusen EJ, Bulstra SK, van der Mei HC, Busscher HJ. Biofilms in chronic diabetic foot ulcers--a study of 2 cases. Acta Orthop. 2011 Jun;82(3):383-5. doi: 10.3109/17453674.2011.581265. Epub 2011 May 11. No abstract available.
PMID: 21561305
citation: Zhao G, Usui ML, Lippman SI, James GA, Stewart PS, Fleckman P, Olerud JE. Biofilms and Inflammation in Chronic Wounds. Adv Wound Care (New Rochelle). 2013 Sep;2(7):389-399. doi: 10.1089/wound.2012.0381.
PMID: 24527355
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: Sashwati Roy
investigator title: Professor
mesh term: Bacterial Infections
mesh term: Wounds and Injuries
sharing ipd: No