<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/NCT03042923</url>
  </required_header>
  <id_info>
    <org_study_id>16-029</org_study_id>
    <nct_id>NCT03042923</nct_id>
  </id_info>
  <brief_title>Intestinal Permeability and Endometriosis</brief_title>
  <official_title>Intestinal Permeability and Endometriosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Tennessee</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Tennessee</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this project will be to determine whether patients with a surgical diagnosis&#xD;
      of endometriosis have impaired intestinal permeability as compared with healthy controls.&#xD;
      This would suggest the presence of an environmentally triggered and intestinally mediated&#xD;
      association in the etiology of endometriosis. This would be a proof of concept trial to&#xD;
      establish whether there is in fact a relationship worthy of future research.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Twenty patients with a clinical diagnosis of endometriosis who are scheduled for surgical&#xD;
      evaluation will be eligible for the study arm of the research. Ten women without history of&#xD;
      autoimmune disease or pelvic pain will serve as controls.&#xD;
&#xD;
      Study subjects will undergo testing for intestinal permeability a week or more before their&#xD;
      scheduled surgery. Both controls and pain patients will be tested for permeability using a&#xD;
      lactulose:mannitol (L:M) oral challenge. Each subject will ingest an oral preparation of&#xD;
      Lactulose 5 gm, Mannitol 1gm and water. This preparation is available as a test kit through&#xD;
      Genova Diagnostics labs. Erlanger Hospital lab does not have a test for measuring urinary&#xD;
      excretion of L:M, or other method of assessing intestinal permeability.&#xD;
&#xD;
      Urine is collected over six hours and is then measured for ratio of L:M. An L:M ratio &gt;0.10&#xD;
      is consistent with increased intestinal permeability. Normally the gut does not absorb&#xD;
      lactulose unless permeability is present. NSAIDS and alcohol increase intestinal&#xD;
      permeability; therefore subjects will be asked to avoid the use of NSAIDS and alcoholic&#xD;
      beverages for a week prior to the test.&#xD;
&#xD;
      Following the L:M testing, the patients who have been enrolled will undergo surgery as&#xD;
      planned. The surgeons should be blinded to the results of the L:M testing until after the&#xD;
      surgery. It is assumed that some of the patients will have surgical evidence of endometriosis&#xD;
      and some will not. The ultimate categories for analysis will be 1) Pain with biopsy proven&#xD;
      endometriosis, and surgical staging of disease, 2) Pain without surgical evidence of&#xD;
      endometriosis, 3) Control patients with no history of chronic pain, alcoholism, celiac&#xD;
      disease or other autoimmune disease. As a secondary element of this study, correlation to the&#xD;
      presence of interstitial cystitis (IC) will also be assessed as all patients in our practice&#xD;
      who undergo surgical evaluation for chronic pain simultaneously are evaluated for IC by&#xD;
      cystoscopy with hydrodistention.&#xD;
&#xD;
      Data that the investigators will gather includes: demographic, pelvic pain parameters,&#xD;
      information on use of tobacco and alcohol, medical history to exclude autoimmune disease&#xD;
      patients and patients with diabetes, intestinal permeability test results and date of test,&#xD;
      surgical findings, American Society of Reproductive Medicine, ASRM, Endometriosis staging&#xD;
      when applicable, presence of extrapelvic endometriosis, pathology results and presence or&#xD;
      absence of interstitial cystitis.&#xD;
&#xD;
      Because this is an unexplored area of research, preliminary data to demonstrate potential&#xD;
      efficacy before embarking on a prospective trial is essential.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2016</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">June 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>lactulose:mannitol (L:M) oral challenge</measure>
    <time_frame>6 hrs</time_frame>
    <description>Urine is collected over six hours and is then measured for ratio of L:M. An L:M ratio &gt;0.10 is consistent with increased intestinal permeability. Normally the gut does not absorb lactulose unless permeability is present.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Surgical Findings</measure>
    <time_frame>24 hrs</time_frame>
    <description>Pathology reported-- endometriosis or no endometriosis</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">46</enrollment>
  <condition>Endometriosis</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <description>Twenty patients, known to us through care at Women's Surgery Center and the private practice of Dr. R. Scott Furr, will be invited to enroll based on a history of pelvic pain and a plan for surgical evaluation and intervention</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Ten healthy female patients, without pelvic pain or history of autoimmune disease, will be asked to participate as controls.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lactulose:mannitol (L:M) oral challenge</intervention_name>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will be recruited through care at Women's Surgery Center and the private&#xD;
        practice of Dr. R. Scott Furr and through Erlanger Women's Specialty Services and the&#xD;
        practice of Dr. Shanti Mohling. Participants will be invited to enroll based on a history&#xD;
        of pelvic pain and a plan for surgical evaluation and intervention. Ten healthy female&#xD;
        women, without pelvic pain or history of autoimmune disease, will be asked to participate&#xD;
        as controls.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female patients with documented history of pelvic pain for the study arm.&#xD;
&#xD;
          -  Healthy female controls without history consistent with autoimmune disease or pelvic&#xD;
             pain&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Co-morbid autoimmune disease such as Celiac disease, lupus, ankylosing spondylitis,&#xD;
             alcoholism and diabetes which have been shown to exhibit elevated levels of Zonulin&#xD;
             and therefore impaired intestinal permeability. Drinking alcohol and taking NSAIDS&#xD;
             elevate intestinal permeability and would affect data.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shanti Mohling, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT College of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Patti Bush, EdD</last_name>
    <role>Study Director</role>
    <affiliation>UT College of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Garrett Lam, MD</last_name>
    <role>Study Chair</role>
    <affiliation>UT College of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steve Radtke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Erlanger Medical Center</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Surgery Center</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37421</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>WITEBSKY E, ROSE NR, TERPLAN K, PAINE JR, EGAN RW. Chronic thyroiditis and autoimmunization. J Am Med Assoc. 1957 Jul 27;164(13):1439-47. doi: 10.1001/jama.1957.02980130015004. No abstract available.</citation>
    <PMID>13448890</PMID>
  </reference>
  <reference>
    <citation>Eisenberg VH, Zolti M, Soriano D. Is there an association between autoimmunity and endometriosis? Autoimmun Rev. 2012 Sep;11(11):806-14. doi: 10.1016/j.autrev.2012.01.005. Epub 2012 Feb 4.</citation>
    <PMID>22330229</PMID>
  </reference>
  <reference>
    <citation>Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008 Nov;173(5):1243-52. doi: 10.2353/ajpath.2008.080192. Epub 2008 Oct 2.</citation>
    <PMID>18832585</PMID>
  </reference>
  <reference>
    <citation>Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 Jul;1258(1):25-33. doi: 10.1111/j.1749-6632.2012.06538.x.</citation>
    <PMID>22731712</PMID>
  </reference>
  <reference>
    <citation>Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21. doi: 10.1073/pnas.0500178102. Epub 2005 Feb 14.</citation>
    <PMID>15710870</PMID>
  </reference>
  <reference>
    <citation>Bjarnason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology. 1995 May;108(5):1566-81. doi: 10.1016/0016-5085(95)90708-4.</citation>
    <PMID>7729650</PMID>
  </reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>April 27, 2020</last_update_submitted>
  <last_update_submitted_qc>April 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intestinal permeability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometriosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mannitol</mesh_term>
    <mesh_term>Lactulose</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/NCT03042923
org study id: 16-029
nct id: NCT03042923
lead sponsor: 
has dmc: No
The objective of this project will be to determine whether patients with a surgical diagnosis
      of endometriosis have impaired intestinal permeability as compared with healthy controls.
      This would suggest the presence of an environmentally triggered and intestinally mediated
      association in the etiology of endometriosis. This would be a proof of concept trial to
      establish whether there is in fact a relationship worthy of future research.
Twenty patients with a clinical diagnosis of endometriosis who are scheduled for surgical
      evaluation will be eligible for the study arm of the research. Ten women without history of
      autoimmune disease or pelvic pain will serve as controls.

      Study subjects will undergo testing for intestinal permeability a week or more before their
      scheduled surgery. Both controls and pain patients will be tested for permeability using a
      lactulose:mannitol (L:M) oral challenge. Each subject will ingest an oral preparation of
      Lactulose 5 gm, Mannitol 1gm and water. This preparation is available as a test kit through
      Genova Diagnostics labs. Erlanger Hospital lab does not have a test for measuring urinary
      excretion of L:M, or other method of assessing intestinal permeability.

      Urine is collected over six hours and is then measured for ratio of L:M. An L:M ratio >0.10
      is consistent with increased intestinal permeability. Normally the gut does not absorb
      lactulose unless permeability is present. NSAIDS and alcohol increase intestinal
      permeability; therefore subjects will be asked to avoid the use of NSAIDS and alcoholic
      beverages for a week prior to the test.

      Following the L:M testing, the patients who have been enrolled will undergo surgery as
      planned. The surgeons should be blinded to the results of the L:M testing until after the
      surgery. It is assumed that some of the patients will have surgical evidence of endometriosis
      and some will not. The ultimate categories for analysis will be 1) Pain with biopsy proven
      endometriosis, and surgical staging of disease, 2) Pain without surgical evidence of
      endometriosis, 3) Control patients with no history of chronic pain, alcoholism, celiac
      disease or other autoimmune disease. As a secondary element of this study, correlation to the
      presence of interstitial cystitis (IC) will also be assessed as all patients in our practice
      who undergo surgical evaluation for chronic pain simultaneously are evaluated for IC by
      cystoscopy with hydrodistention.

      Data that the investigators will gather includes: demographic, pelvic pain parameters,
      information on use of tobacco and alcohol, medical history to exclude autoimmune disease
      patients and patients with diabetes, intestinal permeability test results and date of test,
      surgical findings, American Society of Reproductive Medicine, ASRM, Endometriosis staging
      when applicable, presence of extrapelvic endometriosis, pathology results and presence or
      absence of interstitial cystitis.

      Because this is an unexplored area of research, preliminary data to demonstrate potential
      efficacy before embarking on a prospective trial is essential.
observational model: Case-Control
time perspective: Prospective
measure: lactulose:mannitol (L:M) oral challenge
time frame: 6 hrs
description: Urine is collected over six hours and is then measured for ratio of L:M. An L:M ratio >0.10 is consistent with increased intestinal permeability. Normally the gut does not absorb lactulose unless permeability is present.
measure: Surgical Findings
time frame: 24 hrs
description: Pathology reported-- endometriosis or no endometriosis
arm group label: Treatment
description: Twenty patients, known to us through care at Women's Surgery Center and the private practice of Dr. R. Scott Furr, will be invited to enroll based on a history of pelvic pain and a plan for surgical evaluation and intervention
arm group label: Control
description: Ten healthy female patients, without pelvic pain or history of autoimmune disease, will be asked to participate as controls.
intervention type: Drug
intervention name: lactulose:mannitol (L:M) oral challenge
arm group label: Control
arm group label: Treatment
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shanti Mohling, MD
role: Principal Investigator
affiliation: UT College of Medicine
last name: Patti Bush, EdD
role: Study Director
affiliation: UT College of Medicine
last name: Garrett Lam, MD
role: Study Chair
affiliation: UT College of Medicine
last name: Steve Radtke, MD
role: Principal Investigator
affiliation: UT College of Medicine
facility: 
facility: 
country: United States
citation: WITEBSKY E, ROSE NR, TERPLAN K, PAINE JR, EGAN RW. Chronic thyroiditis and autoimmunization. J Am Med Assoc. 1957 Jul 27;164(13):1439-47. doi: 10.1001/jama.1957.02980130015004. No abstract available.
PMID: 13448890
citation: Eisenberg VH, Zolti M, Soriano D. Is there an association between autoimmunity and endometriosis? Autoimmun Rev. 2012 Sep;11(11):806-14. doi: 10.1016/j.autrev.2012.01.005. Epub 2012 Feb 4.
PMID: 22330229
citation: Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008 Nov;173(5):1243-52. doi: 10.2353/ajpath.2008.080192. Epub 2008 Oct 2.
PMID: 18832585
citation: Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 Jul;1258(1):25-33. doi: 10.1111/j.1749-6632.2012.06538.x.
PMID: 22731712
citation: Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21. doi: 10.1073/pnas.0500178102. Epub 2005 Feb 14.
PMID: 15710870
citation: Bjarnason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology. 1995 May;108(5):1566-81. doi: 10.1016/0016-5085(95)90708-4.
PMID: 7729650
responsible party type: Sponsor
mesh term: Endometriosis
mesh term: Mannitol
mesh term: Lactulose
sharing ipd: No