<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/NCT02259309</url>
  </required_header>
  <id_info>
    <org_study_id>140667</org_study_id>
    <nct_id>NCT02259309</nct_id>
  </id_info>
  <brief_title>Immune Modulation by Misoprostol</brief_title>
  <official_title>Immune Modulation by Misoprostol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gynuity Health Projects</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study is designed to address the null hypothesis that there is no difference in&#xD;
      the local and systemic immunomodulatory effects of buccally or vaginally administered&#xD;
      misoprostol in healthy, reproductive-age women.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of misoprostol drug levels in patients after vaginal and buccal administration</measure>
    <time_frame>Peripheral blood collected at Days 0, 1, 28, and 29</time_frame>
    <description>Peripheral blood collected at Days 0, 1, 28, and 29</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparison of cytokine and chemokine levels in patients after vaginal and buccal administration</measure>
    <time_frame>Peripheral blood collected at Days 0, 1, 28, and 29</time_frame>
    <description>Peripheral blood collected at Days 0, 1, 28, and 29</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of immune cell activation state after vaginal and buccal administration</measure>
    <time_frame>Peripheral blood collected at Days 0, 1, 28, and 29</time_frame>
    <description>Peripheral blood collected at Days 0, 1, 28, and 29</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparison of misoprostol drug levels in patients after vaginal and buccal administration</measure>
    <time_frame>Cervicovaginal lavage at Days 0, 1, 28, and 29</time_frame>
    <description>Cervicovaginal lavage at Days 0, 1, 28, and 29</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparison of cytokine and chemokine levels in patients after vaginal and buccal administration</measure>
    <time_frame>Cervicovaginal lavage at Days 0, 1, 28, and 29</time_frame>
    <description>Cervicovaginal lavage at Days 0, 1, 28, and 29</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of immune cell activation state after vaginal and buccal administration</measure>
    <time_frame>Cervical cytobrush at Days 0, 1, 28, and 29</time_frame>
    <description>Cervical cytobrush at Days 0, 1, 28, and 29</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sequencing of 16S rRNA gene for microbial ecology studies after vaginal and buccal administration</measure>
    <time_frame>Vaginal swab at Days 0, 1, 28, and 29</time_frame>
    <description>Vaginal swab at Days 0, 1, 28, and 29</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Gynecological Infection</condition>
  <arm_group>
    <arm_group_label>Misoprostol administration - buccal then vaginal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaginal or buccal administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Misoprostol administration - vaginal then buccal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaginal or buccal administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Misoprostol - buccal</intervention_name>
    <description>buccal administration</description>
    <arm_group_label>Misoprostol administration - buccal then vaginal</arm_group_label>
    <arm_group_label>Misoprostol administration - vaginal then buccal</arm_group_label>
    <other_name>Cytotec</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Misoprostol - vaginal</intervention_name>
    <description>vaginal administration</description>
    <arm_group_label>Misoprostol administration - buccal then vaginal</arm_group_label>
    <arm_group_label>Misoprostol administration - vaginal then buccal</arm_group_label>
    <other_name>Cytotec</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy women 18-45 years of age&#xD;
&#xD;
          -  Negative result of urine pregnancy test at screening and prior to each administration&#xD;
             of study drug&#xD;
&#xD;
          -  Normal, regularly occurring menses (being 25-35 day cycles)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of hormonal contraception (current or past 3 months)&#xD;
&#xD;
          -  Use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin within two weeks&#xD;
             prior to enrollment or planned use of these medications during the study period&#xD;
&#xD;
          -  Allergy to prostaglandins&#xD;
&#xD;
          -  Previous cervical cancer&#xD;
&#xD;
          -  Partial or complete cervical excision&#xD;
&#xD;
          -  Previous hysterectomy&#xD;
&#xD;
          -  Immunosuppression: either pharmacological or due to comorbidities&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Auto-immune disease&#xD;
&#xD;
          -  History of lymphoma or leukemia&#xD;
&#xD;
          -  Sexually transmitted infection (by self-report) over previous 1 year&#xD;
&#xD;
          -  Bacterial Vaginosis or Candidiasis (current or past 3 months)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David M. Aronoff, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Moran M, Mozes MF, Maddux MS, Veremis S, Bartkus C, Ketel B, Pollak R, Wallemark C, Jonasson O. Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone. N Engl J Med. 1990 Apr 26;322(17):1183-8. doi: 10.1056/NEJM199004263221703.</citation>
    <PMID>2109195</PMID>
  </reference>
  <reference>
    <citation>Pouteil-Noble C, Chapuis F, Berra N, Hadj-Aissa A, Lacavalerie B, Lefrancois N, Martin X, Touraine JL. Misoprostol in renal transplant recipients: a prospective, randomized, controlled study on the prevention of acute rejection episodes and cyclosporin A nephrotoxicity. Nephrol Dial Transplant. 1994;9(5):552-5. doi: 10.1093/ndt/9.5.552.</citation>
    <PMID>8090337</PMID>
  </reference>
  <reference>
    <citation>Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol. 1997 Jul;90(1):88-92. doi: 10.1016/S0029-7844(97)00111-7.</citation>
    <PMID>9207820</PMID>
  </reference>
  <reference>
    <citation>Waiser J, Bohler T, Stoll J, Schumann B, Budde K, Neumayer HH. The immunosuppressive potential of misoprostol--efficacy and variability. Clin Immunol. 2003 Dec;109(3):288-94. doi: 10.1016/j.clim.2003.08.009.</citation>
    <PMID>14697743</PMID>
  </reference>
  <reference>
    <citation>Middleton T, Schaff E, Fielding SL, Scahill M, Shannon C, Westheimer E, Wilkinson T, Winikoff B. Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception. 2005 Nov;72(5):328-32. doi: 10.1016/j.contraception.2005.05.017. Epub 2005 Aug 9.</citation>
    <PMID>16246656</PMID>
  </reference>
  <reference>
    <citation>Tang OS, Ho PC. The pharmacokinetics and different regimens of misoprostol in early first-trimester medical abortion. Contraception. 2006 Jul;74(1):26-30. doi: 10.1016/j.contraception.2006.03.005. Epub 2006 Apr 27.</citation>
    <PMID>16781256</PMID>
  </reference>
  <reference>
    <citation>el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med. 1995 Apr 13;332(15):983-7. doi: 10.1056/NEJM199504133321502.</citation>
    <PMID>7885426</PMID>
  </reference>
  <reference>
    <citation>Ho PC, Ngai SW, Liu KL, Wong GC, Lee SW. Vaginal misoprostol compared with oral misoprostol in termination of second-trimester pregnancy. Obstet Gynecol. 1997 Nov;90(5):735-8. doi: 10.1016/S0029-7844(97)00419-5.</citation>
    <PMID>9351755</PMID>
  </reference>
  <reference>
    <citation>Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, Geis GS. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Aug 15;123(4):241-9. doi: 10.7326/0003-4819-123-4-199508150-00001.</citation>
    <PMID>7611589</PMID>
  </reference>
  <reference>
    <citation>Herting RL, Clay GA. Overview of clinical safety with misoprostol. Dig Dis Sci. 1985 Nov;30(11 Suppl):185S-193S. doi: 10.1007/BF01309407.</citation>
    <PMID>3932053</PMID>
  </reference>
  <reference>
    <citation>Wildeman RA. Focus on misoprostol: review of worldwide safety data. Clin Invest Med. 1987 May;10(3):243-5.</citation>
    <PMID>3113801</PMID>
  </reference>
  <reference>
    <citation>Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, McGowan J. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002;(4):CD002296. doi: 10.1002/14651858.CD002296.</citation>
    <PMID>12519573</PMID>
  </reference>
  <reference>
    <citation>Chong E, Tsereteli T, Nguyen NN, Winikoff B. A randomized controlled trial of different buccal misoprostol doses in mifepristone medical abortion. Contraception. 2012 Sep;86(3):251-6. doi: 10.1016/j.contraception.2011.12.012. Epub 2012 Feb 2.</citation>
    <PMID>22305917</PMID>
  </reference>
  <reference>
    <citation>Raymond EG, Shannon C, Weaver MA, Winikoff B. First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review. Contraception. 2013 Jan;87(1):26-37. doi: 10.1016/j.contraception.2012.06.011. Epub 2012 Aug 13.</citation>
    <PMID>22898359</PMID>
  </reference>
  <reference>
    <citation>Kotsonis FN, Dodd DC, Regnier B, Kohn FE. Preclinical toxicology profile of misoprostol. Dig Dis Sci. 1985 Nov;30(11 Suppl):142S-146S. doi: 10.1007/BF01309401.</citation>
    <PMID>3932047</PMID>
  </reference>
  <reference>
    <citation>Zane S, Guarner J. Gynecologic clostridial toxic shock in women of reproductive age. Curr Infect Dis Rep. 2011 Dec;13(6):561-70. doi: 10.1007/s11908-011-0207-7.</citation>
    <PMID>21882086</PMID>
  </reference>
  <reference>
    <citation>Fjerstad M, Trussell J, Sivin I, Lichtenberg ES, Cullins V. Rates of serious infection after changes in regimens for medical abortion. N Engl J Med. 2009 Jul 9;361(2):145-51. doi: 10.1056/NEJMoa0809146.</citation>
    <PMID>19587339</PMID>
  </reference>
  <reference>
    <citation>Hemmerling A. The safety of misoprostol. ELSEVIER IRELAND LTD; 2006.</citation>
  </reference>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <last_update_submitted>January 12, 2016</last_update_submitted>
  <last_update_submitted_qc>January 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>David Aronoff</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>misoprostol</keyword>
  <keyword>mucosal</keyword>
  <keyword>cervical</keyword>
  <keyword>immune</keyword>
  <keyword>buccal</keyword>
  <keyword>vaginal</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Misoprostol</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/NCT02259309
org study id: 140667
nct id: NCT02259309
lead sponsor: 
collaborator: 
has dmc: No
The present study is designed to address the null hypothesis that there is no difference in
      the local and systemic immunomodulatory effects of buccally or vaginally administered
      misoprostol in healthy, reproductive-age women.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Comparison of misoprostol drug levels in patients after vaginal and buccal administration
time frame: Peripheral blood collected at Days 0, 1, 28, and 29
description: Peripheral blood collected at Days 0, 1, 28, and 29
measure: Comparison of cytokine and chemokine levels in patients after vaginal and buccal administration
time frame: Peripheral blood collected at Days 0, 1, 28, and 29
description: Peripheral blood collected at Days 0, 1, 28, and 29
measure: Determination of immune cell activation state after vaginal and buccal administration
time frame: Peripheral blood collected at Days 0, 1, 28, and 29
description: Peripheral blood collected at Days 0, 1, 28, and 29
measure: Comparison of misoprostol drug levels in patients after vaginal and buccal administration
time frame: Cervicovaginal lavage at Days 0, 1, 28, and 29
description: Cervicovaginal lavage at Days 0, 1, 28, and 29
measure: Comparison of cytokine and chemokine levels in patients after vaginal and buccal administration
time frame: Cervicovaginal lavage at Days 0, 1, 28, and 29
description: Cervicovaginal lavage at Days 0, 1, 28, and 29
measure: Determination of immune cell activation state after vaginal and buccal administration
time frame: Cervical cytobrush at Days 0, 1, 28, and 29
description: Cervical cytobrush at Days 0, 1, 28, and 29
measure: Sequencing of 16S rRNA gene for microbial ecology studies after vaginal and buccal administration
time frame: Vaginal swab at Days 0, 1, 28, and 29
description: Vaginal swab at Days 0, 1, 28, and 29
arm group label: Misoprostol administration - buccal then vaginal
arm group type: Experimental
description: Vaginal or buccal administration
arm group label: Misoprostol administration - vaginal then buccal
arm group type: Experimental
description: Vaginal or buccal administration
intervention type: Drug
intervention name: Misoprostol - buccal
description: buccal administration
arm group label: Misoprostol administration - buccal then vaginal
arm group label: Misoprostol administration - vaginal then buccal
other name: Cytotec
intervention type: Drug
intervention name: Misoprostol - vaginal
description: vaginal administration
arm group label: Misoprostol administration - buccal then vaginal
arm group label: Misoprostol administration - vaginal then buccal
other name: Cytotec
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David M. Aronoff, MD
role: Principal Investigator
affiliation: Vanderbilt University
facility: 
country: United States
citation: Moran M, Mozes MF, Maddux MS, Veremis S, Bartkus C, Ketel B, Pollak R, Wallemark C, Jonasson O. Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone. N Engl J Med. 1990 Apr 26;322(17):1183-8. doi: 10.1056/NEJM199004263221703.
PMID: 2109195
citation: Pouteil-Noble C, Chapuis F, Berra N, Hadj-Aissa A, Lacavalerie B, Lefrancois N, Martin X, Touraine JL. Misoprostol in renal transplant recipients: a prospective, randomized, controlled study on the prevention of acute rejection episodes and cyclosporin A nephrotoxicity. Nephrol Dial Transplant. 1994;9(5):552-5. doi: 10.1093/ndt/9.5.552.
PMID: 8090337
citation: Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol. 1997 Jul;90(1):88-92. doi: 10.1016/S0029-7844(97)00111-7.
PMID: 9207820
citation: Waiser J, Bohler T, Stoll J, Schumann B, Budde K, Neumayer HH. The immunosuppressive potential of misoprostol--efficacy and variability. Clin Immunol. 2003 Dec;109(3):288-94. doi: 10.1016/j.clim.2003.08.009.
PMID: 14697743
citation: Middleton T, Schaff E, Fielding SL, Scahill M, Shannon C, Westheimer E, Wilkinson T, Winikoff B. Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception. 2005 Nov;72(5):328-32. doi: 10.1016/j.contraception.2005.05.017. Epub 2005 Aug 9.
PMID: 16246656
citation: Tang OS, Ho PC. The pharmacokinetics and different regimens of misoprostol in early first-trimester medical abortion. Contraception. 2006 Jul;74(1):26-30. doi: 10.1016/j.contraception.2006.03.005. Epub 2006 Apr 27.
PMID: 16781256
citation: el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med. 1995 Apr 13;332(15):983-7. doi: 10.1056/NEJM199504133321502.
PMID: 7885426
citation: Ho PC, Ngai SW, Liu KL, Wong GC, Lee SW. Vaginal misoprostol compared with oral misoprostol in termination of second-trimester pregnancy. Obstet Gynecol. 1997 Nov;90(5):735-8. doi: 10.1016/S0029-7844(97)00419-5.
PMID: 9351755
citation: Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, Geis GS. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Aug 15;123(4):241-9. doi: 10.7326/0003-4819-123-4-199508150-00001.
PMID: 7611589
citation: Herting RL, Clay GA. Overview of clinical safety with misoprostol. Dig Dis Sci. 1985 Nov;30(11 Suppl):185S-193S. doi: 10.1007/BF01309407.
PMID: 3932053
citation: Wildeman RA. Focus on misoprostol: review of worldwide safety data. Clin Invest Med. 1987 May;10(3):243-5.
PMID: 3113801
citation: Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, McGowan J. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002;(4):CD002296. doi: 10.1002/14651858.CD002296.
PMID: 12519573
citation: Chong E, Tsereteli T, Nguyen NN, Winikoff B. A randomized controlled trial of different buccal misoprostol doses in mifepristone medical abortion. Contraception. 2012 Sep;86(3):251-6. doi: 10.1016/j.contraception.2011.12.012. Epub 2012 Feb 2.
PMID: 22305917
citation: Raymond EG, Shannon C, Weaver MA, Winikoff B. First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review. Contraception. 2013 Jan;87(1):26-37. doi: 10.1016/j.contraception.2012.06.011. Epub 2012 Aug 13.
PMID: 22898359
citation: Kotsonis FN, Dodd DC, Regnier B, Kohn FE. Preclinical toxicology profile of misoprostol. Dig Dis Sci. 1985 Nov;30(11 Suppl):142S-146S. doi: 10.1007/BF01309401.
PMID: 3932047
citation: Zane S, Guarner J. Gynecologic clostridial toxic shock in women of reproductive age. Curr Infect Dis Rep. 2011 Dec;13(6):561-70. doi: 10.1007/s11908-011-0207-7.
PMID: 21882086
citation: Fjerstad M, Trussell J, Sivin I, Lichtenberg ES, Cullins V. Rates of serious infection after changes in regimens for medical abortion. N Engl J Med. 2009 Jul 9;361(2):145-51. doi: 10.1056/NEJMoa0809146.
PMID: 19587339
citation: Hemmerling A. The safety of misoprostol. ELSEVIER IRELAND LTD; 2006.
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: David Aronoff
investigator title: MD
mesh term: Misoprostol