<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/NCT03793062</url>
  </required_header>
  <id_info>
    <org_study_id>1809585623</org_study_id>
    <nct_id>NCT03793062</nct_id>
  </id_info>
  <brief_title>Genetic and Epigenetic Basis of Chronic Wounds</brief_title>
  <official_title>Genetic and Epigenetic Basis of Chronic Wounds</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chandan Sen</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>
      This pilot study is designed for chronic wounds that fail to heal in a timely manner carry&#xD;
      specific genetic signatures. These genetic signatures will be studied using debrided wound&#xD;
      tissue that is removed by the wound care provider as part of standard of care. The reference&#xD;
      genomic signature will be evaluated by obtaining blood samples and will be compared with&#xD;
      wound debrided tissue genomic signature to understand wound specific genomic changes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic wounds affect a large fraction of the world population and poses major threat to the&#xD;
      public health and economy of the United States affecting 6.5 million patients. It has been&#xD;
      estimated that approximately 2% of the population residing in developed countries, will&#xD;
      experience at least one chronic wound during their lifetime. Current treatment options for&#xD;
      chronic wounds are insufficient due to lack of individual specific genetic information. To&#xD;
      improve therapy, an increase in the investigator's understanding of the genetic&#xD;
      predisposition of individuals which result in impaired wound healing response is warranted.&#xD;
      Information about these individual specific genetic and epigenetic regulations can altogether&#xD;
      yield subset of repair genes which can serve as master regulators of wound healing. The&#xD;
      effect of specific genetic information is also modified a lot by environmental epigenetic&#xD;
      factors. Epigenetic changes have been shown to control the wound healing outcomes.&#xD;
&#xD;
      In this prospective pilot study, patients with chronic wounds visiting Indiana University/IU&#xD;
      Health clinics/ hospitals will be enrolled. Patients enrolled in the study will be followed&#xD;
      for 16 weeks. Within this time, debrided wound tissue will be collected, when available, as&#xD;
      part of their standard of care at the clinics. The study consists of two study visits (week 1&#xD;
      and week 16 or earlier if target would is healed before that time). Study visit 1 consists of&#xD;
      obtaining informed consent, medical history, current medications, and baseline demographics&#xD;
      including, but not limited to: age, gender, zip code, ethnicity/race, marital status,&#xD;
      education level, employment history, household income, number of household member. Digital&#xD;
      imaging along with the collection of a saliva and blood sample will be performed during the&#xD;
      visit. Participants will be asked to complete eight health questionnaires. Study visit two&#xD;
      consists of digital imaging, along with a medication and adverse event review.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 4, 2018</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2025</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>Epigenetic and transcriptome changes in debrided tissue from chronic wounds in healing vs non healing phase .</measure>
    <time_frame>16 weeks or healing whichever comes first</time_frame>
    <description>The wound area (digital planimetry at d0/ 16 week) will classify wounds as heal-high (final 16 week size &lt;40% of initial visit, d0) or heal-low (&gt;60% of initial d0).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Wound specific genetic changes using whole genome approaches.</measure>
    <time_frame>16 weeks or healing whichever comes first</time_frame>
    <description>To characterize wound specific genetic changes (e.g., mutations) using whole genome approaches. Genome from blood cells will be used as reference</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Chronic Wounds</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No Interventions</intervention_name>
    <description>Not applicable - No Interventions</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Wound debrided tissue, Blood, and Saliva samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        50 clinically diagnosed chronic wound patients will be recruited for this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Willing to comply with protocol instructions, including all study visits and study&#xD;
             activities.&#xD;
&#xD;
          -  Chronic wounds or acute wounds scheduled for debridement in &gt;30 days since onset&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals who are deemed unable to understand the procedures, risks and benefits of&#xD;
             the study,(i.e. unable to provide informed consent)&#xD;
&#xD;
          -  Pregnant females&#xD;
&#xD;
          -  Subjects with marked immunodeficiency (HIV/AIDS)&#xD;
&#xD;
          -  Prisoners&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chandan K Sen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IU Health Methodist Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999 Sep 2;341(10):738-46. doi: 10.1056/NEJM199909023411006. No abstract available.</citation>
    <PMID>10471461</PMID>
  </reference>
  <reference>
    <citation>Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009 Nov-Dec;17(6):763-71. doi: 10.1111/j.1524-475X.2009.00543.x.</citation>
    <PMID>19903300</PMID>
  </reference>
  <reference>
    <citation>Crovetti G, Martinelli G, Issi M, Barone M, Guizzardi M, Campanati B, Moroni M, Carabelli A. Platelet gel for healing cutaneous chronic wounds. Transfus Apher Sci. 2004 Apr;30(2):145-51. doi: 10.1016/j.transci.2004.01.004.</citation>
    <PMID>15062754</PMID>
  </reference>
  <reference>
    <citation>Gottrup F. A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am J Surg. 2004 May;187(5A):38S-43S. doi: 10.1016/S0002-9610(03)00303-9.</citation>
    <PMID>15147991</PMID>
  </reference>
  <reference>
    <citation>Ti D, Li M, Fu X, Han W. Causes and consequences of epigenetic regulation in wound healing. Wound Repair Regen. 2014 May-Jun;22(3):305-12. doi: 10.1111/wrr.12160.</citation>
    <PMID>24844330</PMID>
  </reference>
  <reference>
    <citation>Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA. Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ. 2007 Feb;14(2):275-85. doi: 10.1038/sj.cdd.4401979. Epub 2006 Jun 9.</citation>
    <PMID>16763620</PMID>
  </reference>
  <reference>
    <citation>Rahnama F, Shafiei F, Gluckman PD, Mitchell MD, Lobie PE. Epigenetic regulation of human trophoblastic cell migration and invasion. Endocrinology. 2006 Nov;147(11):5275-83. doi: 10.1210/en.2006-0288. Epub 2006 Aug 3.</citation>
    <PMID>16887905</PMID>
  </reference>
  <reference>
    <citation>Zhang W, Shiraishi A, Suzuki A, Zheng X, Kodama T, Ohashi Y. Expression and distribution of tissue transglutaminase in normal and injured rat cornea. Curr Eye Res. 2004 Jan;28(1):37-45. doi: 10.1076/ceyr.28.1.37.23493.</citation>
    <PMID>14704912</PMID>
  </reference>
  <reference>
    <citation>Ai L, Kim WJ, Demircan B, Dyer LM, Bray KJ, Skehan RR, Massoll NA, Brown KD. The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. Carcinogenesis. 2008 Mar;29(3):510-8. doi: 10.1093/carcin/bgm280. Epub 2008 Jan 3.</citation>
    <PMID>18174247</PMID>
  </reference>
  <reference>
    <citation>Chernov AV, Sounni NE, Remacle AG, Strongin AY. Epigenetic control of the invasion-promoting MT1-MMP/MMP-2/TIMP-2 axis in cancer cells. J Biol Chem. 2009 May 8;284(19):12727-34. doi: 10.1074/jbc.M900273200. Epub 2009 Mar 13.</citation>
    <PMID>19286653</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Chandan Sen</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>genome</keyword>
  <keyword>epigenome</keyword>
  <keyword>chronic wounds</keyword>
  <keyword>genetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03793062
org study id: 1809585623
nct id: NCT03793062
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This pilot study is designed for chronic wounds that fail to heal in a timely manner carry
      specific genetic signatures. These genetic signatures will be studied using debrided wound
      tissue that is removed by the wound care provider as part of standard of care. The reference
      genomic signature will be evaluated by obtaining blood samples and will be compared with
      wound debrided tissue genomic signature to understand wound specific genomic changes.
Chronic wounds affect a large fraction of the world population and poses major threat to the
      public health and economy of the United States affecting 6.5 million patients. It has been
      estimated that approximately 2% of the population residing in developed countries, will
      experience at least one chronic wound during their lifetime. Current treatment options for
      chronic wounds are insufficient due to lack of individual specific genetic information. To
      improve therapy, an increase in the investigator's understanding of the genetic
      predisposition of individuals which result in impaired wound healing response is warranted.
      Information about these individual specific genetic and epigenetic regulations can altogether
      yield subset of repair genes which can serve as master regulators of wound healing. The
      effect of specific genetic information is also modified a lot by environmental epigenetic
      factors. Epigenetic changes have been shown to control the wound healing outcomes.

      In this prospective pilot study, patients with chronic wounds visiting Indiana University/IU
      Health clinics/ hospitals will be enrolled. Patients enrolled in the study will be followed
      for 16 weeks. Within this time, debrided wound tissue will be collected, when available, as
      part of their standard of care at the clinics. The study consists of two study visits (week 1
      and week 16 or earlier if target would is healed before that time). Study visit 1 consists of
      obtaining informed consent, medical history, current medications, and baseline demographics
      including, but not limited to: age, gender, zip code, ethnicity/race, marital status,
      education level, employment history, household income, number of household member. Digital
      imaging along with the collection of a saliva and blood sample will be performed during the
      visit. Participants will be asked to complete eight health questionnaires. Study visit two
      consists of digital imaging, along with a medication and adverse event review.
observational model: Cohort
time perspective: Prospective
measure: Epigenetic and transcriptome changes in debrided tissue from chronic wounds in healing vs non healing phase .
time frame: 16 weeks or healing whichever comes first
description: The wound area (digital planimetry at d0/ 16 week) will classify wounds as heal-high (final 16 week size <40% of initial visit, d0) or heal-low (>60% of initial d0).
measure: Wound specific genetic changes using whole genome approaches.
time frame: 16 weeks or healing whichever comes first
description: To characterize wound specific genetic changes (e.g., mutations) using whole genome approaches. Genome from blood cells will be used as reference
intervention type: Other
intervention name: No Interventions
description: Not applicable - No Interventions
Wound debrided tissue, Blood, and Saliva samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Chandan K Sen, PhD
role: Principal Investigator
affiliation: Indiana University
facility: 
country: United States
citation: Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999 Sep 2;341(10):738-46. doi: 10.1056/NEJM199909023411006. No abstract available.
PMID: 10471461
citation: Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009 Nov-Dec;17(6):763-71. doi: 10.1111/j.1524-475X.2009.00543.x.
PMID: 19903300
citation: Crovetti G, Martinelli G, Issi M, Barone M, Guizzardi M, Campanati B, Moroni M, Carabelli A. Platelet gel for healing cutaneous chronic wounds. Transfus Apher Sci. 2004 Apr;30(2):145-51. doi: 10.1016/j.transci.2004.01.004.
PMID: 15062754
citation: Gottrup F. A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am J Surg. 2004 May;187(5A):38S-43S. doi: 10.1016/S0002-9610(03)00303-9.
PMID: 15147991
citation: Ti D, Li M, Fu X, Han W. Causes and consequences of epigenetic regulation in wound healing. Wound Repair Regen. 2014 May-Jun;22(3):305-12. doi: 10.1111/wrr.12160.
PMID: 24844330
citation: Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA. Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ. 2007 Feb;14(2):275-85. doi: 10.1038/sj.cdd.4401979. Epub 2006 Jun 9.
PMID: 16763620
citation: Rahnama F, Shafiei F, Gluckman PD, Mitchell MD, Lobie PE. Epigenetic regulation of human trophoblastic cell migration and invasion. Endocrinology. 2006 Nov;147(11):5275-83. doi: 10.1210/en.2006-0288. Epub 2006 Aug 3.
PMID: 16887905
citation: Zhang W, Shiraishi A, Suzuki A, Zheng X, Kodama T, Ohashi Y. Expression and distribution of tissue transglutaminase in normal and injured rat cornea. Curr Eye Res. 2004 Jan;28(1):37-45. doi: 10.1076/ceyr.28.1.37.23493.
PMID: 14704912
citation: Ai L, Kim WJ, Demircan B, Dyer LM, Bray KJ, Skehan RR, Massoll NA, Brown KD. The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. Carcinogenesis. 2008 Mar;29(3):510-8. doi: 10.1093/carcin/bgm280. Epub 2008 Jan 3.
PMID: 18174247
citation: Chernov AV, Sounni NE, Remacle AG, Strongin AY. Epigenetic control of the invasion-promoting MT1-MMP/MMP-2/TIMP-2 axis in cancer cells. J Biol Chem. 2009 May 8;284(19):12727-34. doi: 10.1074/jbc.M900273200. Epub 2009 Mar 13.
PMID: 19286653
responsible party type: Sponsor-Investigator
investigator affiliation: Indiana University
investigator full name: Chandan Sen
investigator title: Professor
mesh term: Wounds and Injuries
sharing ipd: Undecided