<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/NCT02968459</url>
  </required_header>
  <id_info>
    <org_study_id>MCHHFoshan-1603</org_study_id>
    <nct_id>NCT02968459</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Local Intramuscular Injection for Treatment of Uterine Scars</brief_title>
  <official_title>A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Local Intramuscular Injection for Treatment of Uterine Scars</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maternal and Child Health Hospital of Foshan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maternal and Child Health Hospital of Foshan</source>
  <oversight_info>
    <has_dmc>Yes</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 is a single center, randomized, double blind, placebo controlled study to evaluate the&#xD;
      safety and efficacy of umbilical cord mesenchymal stem cell local intramuscular injection for&#xD;
      treatment of caesarean section uterine scars.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent decades, the percentage of Cesarean section (CS) deliveries has dramatically&#xD;
      increased around the world. While it allows safe delivery in many situations, the risks of&#xD;
      severe maternal complications associated with cesarean delivery are higher than those&#xD;
      associated with vaginal delivery. These maternal complications include short term, long-term,&#xD;
      the next pregnancy, and the non-pregnant state, such as abnormal uterine bleeding and&#xD;
      postmenstrual spotting.&#xD;
&#xD;
      Uterine niche, also named cesarean scar defect, deficient cesarean scar, pouch, or&#xD;
      diverticulum, is defined as a triangular anechoic structure at the site of the scar or a gap&#xD;
      in the myometrium at the site of a previous caesarean section. It is one of the most common&#xD;
      complications associated with previous cesarean section. The primary clinical manifestation&#xD;
      is postmenstrual spotting, which may seriously affect the daily life of patients. The&#xD;
      treatment includes medical treatment, such as oral contraceptives, and surgical methods, such&#xD;
      as hysteroscopy resectoscopic correction, endometrial ablation, laparoscopic surgery, and&#xD;
      transvaginal repair surgery. Although good outcomes are reported in each study, present&#xD;
      treatments could not decrease the incidence among women after undergoing cesarean section.&#xD;
&#xD;
      Mesenchymal stem cells (MSCs) are long-lived cells with the ability of both self-renewal and&#xD;
      differentiation into multi-potential cells, such as osteoblasts, adipocytes and smooth muscle&#xD;
      cells. Trials with MSCs in patients after myocardial infarction have shown an excellent&#xD;
      safety and efficacy. In this trial, the investigators postulate that MSCs can reduce uterine&#xD;
      niche and convert scar tissue to viable myometrium. To test the hypothesis, the investigators&#xD;
      therefore undertake a Phase II clinical trial of the treatment for uterine niche among&#xD;
      primiparous women who undergo cesarean section.&#xD;
&#xD;
      This is a randomized, double-blind, placebo-controlled clinical trial designed to investigate&#xD;
      the efficacy and safety of umbilical cord mesenchymal stem cells treatment on the caesarean&#xD;
      section uterine scars. A total of one hundred and twenty (120) participants will be&#xD;
      randomized (1:1) to receive direct local intramuscular injection of 1*10^7 MSCs (a dose of&#xD;
      1*10^7 cells in 1 ml of 0.9% saline) (MSCs group) or an identical-appearing 1ml of 0.9%&#xD;
      saline placebo (placebo-controlled group). Cesarean procedures and care will follow usual&#xD;
      practices. All participants will be performed by obstetricians from the investigators'&#xD;
      department using a unified double-layer uterine closure technique with a continuous&#xD;
      absorbable polyglycolic 1-0 suture. After suturing the uterine incision, direct local&#xD;
      intramuscular injection will be performed in the uterine incision as soon as possible on the&#xD;
      operating table. One ml solution will be injected as twenty aliquots of 0.05ml into each&#xD;
      injection site on the incision. Injection sites will be selected near the incision at evenly&#xD;
      20 different sites. Participants will be followed up at 6 weeks, 3 months and 6 months. For&#xD;
      the purpose of the endpoint analysis and safety evaluations, the investigators will utilize&#xD;
      an &quot;intention-to-treat&quot; study population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The pandemic resulted in no enrollments.&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 2021</start_date>
  <completion_date type="Anticipated">April 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with uterine niche</measure>
    <time_frame>6 months post treatment</time_frame>
    <description>The niche is defined as a triangular anechoic area at the presumed site of incision in the uterus by transvaginal utrasonography.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of uterine scar thickness</measure>
    <time_frame>6 weeks, 3 and 6 months post treatment</time_frame>
    <description>The scar thickness be measured using a transvaginal utrasonography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of uterine scar area</measure>
    <time_frame>6 weeks, 3 and 6 months post treatment</time_frame>
    <description>The scar area will be measured using a transvaginal utrasonography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with endometritis</measure>
    <time_frame>6 months post treatment</time_frame>
    <description>Endometritis is defined as the presence of at least two of the following signs with no other recognized cause: fever (temperature of at least 38℃), abdominal pain, uterine tenderness, or purulent drainage from the uterus.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with wound infection</measure>
    <time_frame>6 months post treatment</time_frame>
    <description>Wound infection is defined as the presence of either superficial or deep incisional surgical-site infection characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision site with or without fever and included necrotizing fasciitis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunoglobulin concentrations in breast milk and serum</measure>
    <time_frame>6 weeks, 3 and 6 months post treatment</time_frame>
    <description>Breast milk and serum immunoglobulin (IgG, IgA, IgM) and the complement (C3, C4) are detected by transmission immune turbidity method using automatic biochemical analyzer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events occurrence</measure>
    <time_frame>6 months post treatment</time_frame>
    <description>Adverse events will be evaluated since the baseline visit until 6 months after the end of the treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Uterine Scar</condition>
  <arm_group>
    <arm_group_label>Umbilical cord MSCs Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1*10^7 Umbilical cord MSCs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo-Controlled Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1ml of 0.9% saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Umbilical cord MSCs</intervention_name>
    <description>Participants will receive direct local intramuscular injection of 1*10^7 MSCs (in 1ml of 0.9% saline) in the uterine incision.</description>
    <arm_group_label>Umbilical cord MSCs Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>0.9% Saline</intervention_name>
    <description>Participants will receive direct local intramuscular injection 1ml of 0.9% saline in the uterine incision.</description>
    <arm_group_label>Placebo-Controlled Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primiparous women receiving cesarean delivery&#xD;
&#xD;
          -  Ages between 21-35 years&#xD;
&#xD;
          -  Gestation ages ≥ 37 weeks and &lt; 42 weeks&#xD;
&#xD;
          -  Willing to comply with study dosing and completed the entire course of the study&#xD;
&#xD;
          -  Willing to give and sign an informed consent form and a photographic release form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fibroids&#xD;
&#xD;
          -  Placenta previa&#xD;
&#xD;
          -  Placenta abruption&#xD;
&#xD;
          -  Multiple gestation&#xD;
&#xD;
          -  Antepartum hemorrhage&#xD;
&#xD;
          -  Preeclampsia/Eclampsia&#xD;
&#xD;
          -  Hepatic or renal dysfunction&#xD;
&#xD;
          -  Any systemic uncontrolled disease&#xD;
&#xD;
          -  Inability to provide consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhengping Liu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maternal and Child Health Hospital of Foshan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maternal and Child Health Hospital of Foshan</name>
      <address>
        <city>Foshan</city>
        <state>Guangdong</state>
        <zip>528000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Fan D, Wu S, Ye S, Wang W, Guo X, Liu Z. Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial. Medicine (Baltimore). 2017 Nov;96(44):e8480. doi: 10.1097/MD.0000000000008480.</citation>
    <PMID>29095305</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Maternal and Child Health Hospital of Foshan</investigator_affiliation>
    <investigator_full_name>Zhengping Liu, MD</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>Mesenchymal Stem Cells</keyword>
  <keyword>Cesarean Section</keyword>
  <keyword>Uterine Scar</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cicatrix</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/NCT02968459
org study id: MCHHFoshan-1603
nct id: NCT02968459
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single center, randomized, double blind, placebo controlled study to evaluate the
      safety and efficacy of umbilical cord mesenchymal stem cell local intramuscular injection for
      treatment of caesarean section uterine scars.
In recent decades, the percentage of Cesarean section (CS) deliveries has dramatically
      increased around the world. While it allows safe delivery in many situations, the risks of
      severe maternal complications associated with cesarean delivery are higher than those
      associated with vaginal delivery. These maternal complications include short term, long-term,
      the next pregnancy, and the non-pregnant state, such as abnormal uterine bleeding and
      postmenstrual spotting.

      Uterine niche, also named cesarean scar defect, deficient cesarean scar, pouch, or
      diverticulum, is defined as a triangular anechoic structure at the site of the scar or a gap
      in the myometrium at the site of a previous caesarean section. It is one of the most common
      complications associated with previous cesarean section. The primary clinical manifestation
      is postmenstrual spotting, which may seriously affect the daily life of patients. The
      treatment includes medical treatment, such as oral contraceptives, and surgical methods, such
      as hysteroscopy resectoscopic correction, endometrial ablation, laparoscopic surgery, and
      transvaginal repair surgery. Although good outcomes are reported in each study, present
      treatments could not decrease the incidence among women after undergoing cesarean section.

      Mesenchymal stem cells (MSCs) are long-lived cells with the ability of both self-renewal and
      differentiation into multi-potential cells, such as osteoblasts, adipocytes and smooth muscle
      cells. Trials with MSCs in patients after myocardial infarction have shown an excellent
      safety and efficacy. In this trial, the investigators postulate that MSCs can reduce uterine
      niche and convert scar tissue to viable myometrium. To test the hypothesis, the investigators
      therefore undertake a Phase II clinical trial of the treatment for uterine niche among
      primiparous women who undergo cesarean section.

      This is a randomized, double-blind, placebo-controlled clinical trial designed to investigate
      the efficacy and safety of umbilical cord mesenchymal stem cells treatment on the caesarean
      section uterine scars. A total of one hundred and twenty (120) participants will be
      randomized (1:1) to receive direct local intramuscular injection of 1*10^7 MSCs (a dose of
      1*10^7 cells in 1 ml of 0.9% saline) (MSCs group) or an identical-appearing 1ml of 0.9%
      saline placebo (placebo-controlled group). Cesarean procedures and care will follow usual
      practices. All participants will be performed by obstetricians from the investigators'
      department using a unified double-layer uterine closure technique with a continuous
      absorbable polyglycolic 1-0 suture. After suturing the uterine incision, direct local
      intramuscular injection will be performed in the uterine incision as soon as possible on the
      operating table. One ml solution will be injected as twenty aliquots of 0.05ml into each
      injection site on the incision. Injection sites will be selected near the incision at evenly
      20 different sites. Participants will be followed up at 6 weeks, 3 months and 6 months. For
      the purpose of the endpoint analysis and safety evaluations, the investigators will utilize
      an "intention-to-treat" study population.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants with uterine niche
time frame: 6 months post treatment
description: The niche is defined as a triangular anechoic area at the presumed site of incision in the uterus by transvaginal utrasonography.
measure: Change of uterine scar thickness
time frame: 6 weeks, 3 and 6 months post treatment
description: The scar thickness be measured using a transvaginal utrasonography
measure: Change of uterine scar area
time frame: 6 weeks, 3 and 6 months post treatment
description: The scar area will be measured using a transvaginal utrasonography
measure: Number of participants with endometritis
time frame: 6 months post treatment
description: Endometritis is defined as the presence of at least two of the following signs with no other recognized cause: fever (temperature of at least 38℃), abdominal pain, uterine tenderness, or purulent drainage from the uterus.
measure: Number of participants with wound infection
time frame: 6 months post treatment
description: Wound infection is defined as the presence of either superficial or deep incisional surgical-site infection characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision site with or without fever and included necrotizing fasciitis.
measure: Immunoglobulin concentrations in breast milk and serum
time frame: 6 weeks, 3 and 6 months post treatment
description: Breast milk and serum immunoglobulin (IgG, IgA, IgM) and the complement (C3, C4) are detected by transmission immune turbidity method using automatic biochemical analyzer.
measure: Adverse events occurrence
time frame: 6 months post treatment
description: Adverse events will be evaluated since the baseline visit until 6 months after the end of the treatment.
arm group label: Umbilical cord MSCs Group
arm group type: Experimental
description: 1*10^7 Umbilical cord MSCs
arm group label: Placebo-Controlled Group
arm group type: Placebo Comparator
description: 1ml of 0.9% saline
intervention type: Other
intervention name: Umbilical cord MSCs
description: Participants will receive direct local intramuscular injection of 1*10^7 MSCs (in 1ml of 0.9% saline) in the uterine incision.
arm group label: Umbilical cord MSCs Group
intervention type: Other
intervention name: 0.9% Saline
description: Participants will receive direct local intramuscular injection 1ml of 0.9% saline in the uterine incision.
arm group label: Placebo-Controlled Group
criteria: 
gender: Female
minimum age: 21 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Zhengping Liu, MD
role: Principal Investigator
affiliation: Maternal and Child Health Hospital of Foshan
facility: 
country: China
citation: Fan D, Wu S, Ye S, Wang W, Guo X, Liu Z. Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial. Medicine (Baltimore). 2017 Nov;96(44):e8480. doi: 10.1097/MD.0000000000008480.
PMID: 29095305
responsible party type: Principal Investigator
investigator affiliation: Maternal and Child Health Hospital of Foshan
investigator full name: Zhengping Liu, MD
investigator title: Director
mesh term: Cicatrix
sharing ipd: Undecided