<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/NCT01679561</url>
  </required_header>
  <id_info>
    <org_study_id>ILRIFRM</org_study_id>
    <nct_id>NCT01679561</nct_id>
  </id_info>
  <brief_title>Intralipid Therapy for Recurrent Implantation Failure and Recurrent Miscarriages: Is it a Hope or Myth?A Randomized Clinical Trial</brief_title>
  <acronym>ILRIFRM</acronym>
  <official_title>Phase 4 Study of the Efficacy of Intralipid Treatment in Patients With Recurrent Implantation Failure and Miscarriages With High Peripheral and Uterine Natural Killer Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Woman's Health University Hospital, Egypt</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Woman's Health University Hospital, Egypt</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Both organ-specific and systemic autoimmunity are associated with an increased prevalence of&#xD;
      recurrent miscarriage and reproductive failure, rendering the role of the maternal&#xD;
      immunological system in fertility a key concept. It is believed by some that central to this&#xD;
      theme is the maternal cytokine profile, with particularly T-helper (Th) cells. Immune&#xD;
      modulating therapies have therefore been mooted as potential therapeutic strategies. Recent&#xD;
      reports of high pregnancy rates achievable in women with RIF have added fuel to the debate&#xD;
      regarding the effectiveness of intralipids in modulating the immune system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators would like to assess if that intralipids therapy is an effective treatment&#xD;
      for women undergoing repeated failed assisted reproduction cycles and recurrent miscarriages&#xD;
      against traditional methods in randomised clinical trial (RCT).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>February 2012</start_date>
  <completion_date type="Anticipated">December 2013</completion_date>
  <primary_completion_date type="Actual">August 2012</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The effectiveness of intralipid on normalization of nk level and rate of clinical pregnancy .</measure>
    <time_frame>2 ys</time_frame>
    <description>Two hundreds patients (group1) with abnormal NK activity results (NKa)will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipids 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipid 20% diluted in 250 mL saline) infusions and their NKa will be tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 200 patients will receive other routine measures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the rate of continuation of pregnancy beyond 12 weeks of pregnancy,the adverse effects related to the drug.</measure>
    <time_frame>2 ys</time_frame>
    <description>Two hundreds patients (group1) with abnormal NK activity results (NKa) will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipid 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipid 20% diluted in 250 mL saline) infusions and their NKa were tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 200 patients will receive routine measures.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pregnancy Complicated by Low Implantation</condition>
  <arm_group>
    <arm_group_label>intralipids</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two hundreds patients (group1) with abnormal NK activity results (NKa)will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipids 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipids 20% diluted in 250 mL saline) infusions and their NKa will be tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 180 patients will receive placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>intralipid</intervention_name>
    <description>intravenous intralipid 20% is given to the patients known to be have either recurrent failed IVF, RPL</description>
    <arm_group_label>intralipids</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Recurrent unexplained failed IVF, ICSI.&#xD;
&#xD;
          2. Recurrent unexplained miscarriages.&#xD;
&#xD;
          3. High level of peripheral and uterine NK.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age above forty years old.&#xD;
&#xD;
          2. Antiphospholipid syndrome (lupus anticoagulant and/or anticardiolipin antibodies [IgG&#xD;
             or IgM]); other recognised thrombophilic conditions (testing according to usual clinic&#xD;
             practice).&#xD;
&#xD;
          3. Intrauterine abnormalities (as assessed by ultrasound, hysterosonography,&#xD;
             hysterosalpingogram, or hysteroscopy).&#xD;
&#xD;
          4. Fibroids distorting uterine cavity.&#xD;
&#xD;
          5. Abnormal parental karyotype.&#xD;
&#xD;
          6. Other identifiable causes of recurrent miscarriages (tests initiated only if&#xD;
             clinically indicated) e.g., diabetes, thyroid disease and systemic lupus erythematosus&#xD;
             (SLE).&#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>Alaa M Ismail, M D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of medicine,Assiut university,Egypt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Women's Health Hospital</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 20, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 6, 2012</study_first_posted>
  <last_update_submitted>January 6, 2021</last_update_submitted>
  <last_update_submitted_qc>January 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Woman's Health University Hospital, Egypt</investigator_affiliation>
    <investigator_full_name>alaa eldeen mahmoud ismail</investigator_full_name>
    <investigator_title>M D</investigator_title>
  </responsible_party>
  <keyword>implantation failure</keyword>
  <keyword>recurrent abortion</keyword>
  <keyword>intralipid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abortion, Spontaneous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Soybean oil, phospholipid emulsion</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/NCT01679561
org study id: ILRIFRM
nct id: NCT01679561
lead sponsor: 
has dmc: Yes
Both organ-specific and systemic autoimmunity are associated with an increased prevalence of
      recurrent miscarriage and reproductive failure, rendering the role of the maternal
      immunological system in fertility a key concept. It is believed by some that central to this
      theme is the maternal cytokine profile, with particularly T-helper (Th) cells. Immune
      modulating therapies have therefore been mooted as potential therapeutic strategies. Recent
      reports of high pregnancy rates achievable in women with RIF have added fuel to the debate
      regarding the effectiveness of intralipids in modulating the immune system.
The investigators would like to assess if that intralipids therapy is an effective treatment
      for women undergoing repeated failed assisted reproduction cycles and recurrent miscarriages
      against traditional methods in randomised clinical trial (RCT).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The effectiveness of intralipid on normalization of nk level and rate of clinical pregnancy .
time frame: 2 ys
description: Two hundreds patients (group1) with abnormal NK activity results (NKa)will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipids 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipid 20% diluted in 250 mL saline) infusions and their NKa will be tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 200 patients will receive other routine measures.
measure: the rate of continuation of pregnancy beyond 12 weeks of pregnancy,the adverse effects related to the drug.
time frame: 2 ys
description: Two hundreds patients (group1) with abnormal NK activity results (NKa) will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipid 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipid 20% diluted in 250 mL saline) infusions and their NKa were tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 200 patients will receive routine measures.
arm group label: intralipids
arm group type: Experimental
description: Two hundreds patients (group1) with abnormal NK activity results (NKa)will receive intralipids 20% i.v. (9 mg/mL total blood volume -corresponds to 2 mL of intralipids 20% diluted in 250 mL saline; or 18 mg/mL - corresponds to 4 mL of intralipids 20% diluted in 250 mL saline) infusions and their NKa will be tested periodically. The determination of NK cell function will be performed by flow cytometry using K562 cells as targets,then follow up of the patients by the Doppler of endometrial blood follow at the time of luteal phase,and the clinical pregnancy rate.Group(2)of 180 patients will receive placebo.
intervention type: Drug
intervention name: intralipid
description: intravenous intralipid 20% is given to the patients known to be have either recurrent failed IVF, RPL
arm group label: intralipids
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alaa M Ismail, M D
role: Principal Investigator
affiliation: Faculty of medicine,Assiut university,Egypt
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Woman's Health University Hospital, Egypt
investigator full name: alaa eldeen mahmoud ismail
investigator title: M D
mesh term: Abortion, Spontaneous
mesh term: Soybean oil, phospholipid emulsion