<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/NCT03023514</url>
  </required_header>
  <id_info>
    <org_study_id>ALA_ImplRate</org_study_id>
    <nct_id>NCT03023514</nct_id>
  </id_info>
  <brief_title>Lipoic Acid Supplementation in IVF</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lo.Li.Pharma s.r.l</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lo.Li.Pharma s.r.l</source>
  <brief_summary>
    <textblock>
      Alpha-Lipoic Acid (ALA) is a natural molecule that can make a significant contribution to the&#xD;
      success of embryo implantation phase, because it exerts, directly or indirectly, an&#xD;
      immunomodulatory activity. ALA has the ability to regenerate antioxidants molecules that&#xD;
      facilitate embryo implantation, and to stimulate the production of local mediators useful for&#xD;
      implantation. This study is a prospective clinical trial and aims to evaluate the&#xD;
      reproductive outcomes of Italian couples following oocyte donation fresh cycles when&#xD;
      receiving per os tablets of lipoic acid. Indeed, the control group had only the standard&#xD;
      treatment (vaginal progesterone), whereas the study group, in addition to that, received ALA&#xD;
      (300 mg, 2 times per day) by oral route, from the day of donors oocyte pick up until the&#xD;
      pregnancy test. If the childbearing occurred, treatment continued until the 8th week of&#xD;
      pregnancy. Primary outcome of the study is the implantation rate while the positive hCG rate,&#xD;
      the clinical pregnancy rate, the miscarriage rate and the live-birth rate are secondary&#xD;
      outcomes .&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
  </study_design_info>
  <primary_outcome>
    <measure>Number of implants per cycle</measure>
    <time_frame>Within 7 weeks after blastocystis transfer</time_frame>
    <description>Implantation rate is defined as the percentage of transferred embryos that develop at least to the stage of fetal heart activity documented by pregnancy ultrasound.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of biochemical pregnancies per group</measure>
    <time_frame>Within 7 weeks after blastocystis transfer</time_frame>
    <description>Positive β-human chorionic gonadotropin (hCG) test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of clinical pregnancies per group</measure>
    <time_frame>7 weeks of gestation</time_frame>
    <description>A positive β-hCG test and a fetal heart beat seen by ultrasound at 7 weeks of gestation was defined as a clinical pregnancy, otherwise it was considered a biochemical pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of live birth per group</measure>
    <time_frame>At delivery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of miscarriage per group</measure>
    <time_frame>Within 22 weeks of gestation</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">172</enrollment>
  <condition>Women Infertility</condition>
  <arm_group>
    <arm_group_label>ALA + P</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral alpha-lipoic acid + vaginal Progesterone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>P</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>vaginal Progesterone</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Oral Lipoic acid</intervention_name>
    <description>300 mg ALA x2 (1pill orally/12h) to the recipient from the day of the donors pick up until 8 week of pregnancy</description>
    <arm_group_label>ALA + P</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaginal Progesterone</intervention_name>
    <description>200 mg Vaginal Progesterone (1 vaginal capsule/24h) from the day of the donors pick up until 8 week of pregnancy</description>
    <arm_group_label>ALA + P</arm_group_label>
    <arm_group_label>P</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Donors:&#xD;
&#xD;
          -  Proof of fertility;&#xD;
&#xD;
          -  ⩽32 years old&#xD;
&#xD;
          -  BMI &lt;30 kg/m2&#xD;
&#xD;
          -  Regular menstrual cycles of 25-33 days&#xD;
&#xD;
          -  Two normal ovaries based on transvaginal scan findings.&#xD;
&#xD;
        Recipients:&#xD;
&#xD;
          -  Women with infertility problems&#xD;
&#xD;
          -  ⩽50 years old,&#xD;
&#xD;
          -  BMI &lt;34 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Donors:&#xD;
&#xD;
          -  Polycystic ovaries&#xD;
&#xD;
          -  Endometriosis&#xD;
&#xD;
          -  Gynaecological or medical disorders.&#xD;
&#xD;
        Recipients:&#xD;
&#xD;
          -  Endocrinologic problems&#xD;
&#xD;
          -  Medication for chronic illness&#xD;
&#xD;
          -  Azoospermic partner that require TESE&#xD;
&#xD;
          -  Sperm donation cycles&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Iakentro Advanced Medical Centre, IVF Unit</name>
      <address>
        <city>Thessaloniki</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <reference>
    <citation>Monastra G, De Grazia S, Cilaker Micili S, Goker A, Unfer V. Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage. Expert Opin Drug Deliv. 2016 Dec;13(12):1695-1708. doi: 10.1080/17425247.2016.1200556. Epub 2016 Jun 24.</citation>
    <PMID>27292272</PMID>
  </reference>
  <reference>
    <citation>Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012 Dec;18(12):1754-67. doi: 10.1038/nm.3012.</citation>
    <PMID>23223073</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oocyte donation</keyword>
  <keyword>IVF</keyword>
  <keyword>Lipoic acid</keyword>
  <keyword>Implantation rate</keyword>
  <keyword>Endometrial receptivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thioctic Acid</mesh_term>
    <mesh_term>Progesterone</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/NCT03023514
org study id: ALA_ImplRate
nct id: NCT03023514
lead sponsor: 
Alpha-Lipoic Acid (ALA) is a natural molecule that can make a significant contribution to the
      success of embryo implantation phase, because it exerts, directly or indirectly, an
      immunomodulatory activity. ALA has the ability to regenerate antioxidants molecules that
      facilitate embryo implantation, and to stimulate the production of local mediators useful for
      implantation. This study is a prospective clinical trial and aims to evaluate the
      reproductive outcomes of Italian couples following oocyte donation fresh cycles when
      receiving per os tablets of lipoic acid. Indeed, the control group had only the standard
      treatment (vaginal progesterone), whereas the study group, in addition to that, received ALA
      (300 mg, 2 times per day) by oral route, from the day of donors oocyte pick up until the
      pregnancy test. If the childbearing occurred, treatment continued until the 8th week of
      pregnancy. Primary outcome of the study is the implantation rate while the positive hCG rate,
      the clinical pregnancy rate, the miscarriage rate and the live-birth rate are secondary
      outcomes .
allocation: Randomized
measure: Number of implants per cycle
time frame: Within 7 weeks after blastocystis transfer
description: Implantation rate is defined as the percentage of transferred embryos that develop at least to the stage of fetal heart activity documented by pregnancy ultrasound.
measure: Number of biochemical pregnancies per group
time frame: Within 7 weeks after blastocystis transfer
description: Positive β-human chorionic gonadotropin (hCG) test
measure: Number of clinical pregnancies per group
time frame: 7 weeks of gestation
description: A positive β-hCG test and a fetal heart beat seen by ultrasound at 7 weeks of gestation was defined as a clinical pregnancy, otherwise it was considered a biochemical pregnancy.
measure: Number of live birth per group
time frame: At delivery
measure: Number of miscarriage per group
time frame: Within 22 weeks of gestation
arm group label: ALA + P
arm group type: Experimental
description: Oral alpha-lipoic acid + vaginal Progesterone
arm group label: P
arm group type: Active Comparator
description: vaginal Progesterone
intervention type: Dietary Supplement
intervention name: Oral Lipoic acid
description: 300 mg ALA x2 (1pill orally/12h) to the recipient from the day of the donors pick up until 8 week of pregnancy
arm group label: ALA + P
intervention type: Drug
intervention name: Vaginal Progesterone
description: 200 mg Vaginal Progesterone (1 vaginal capsule/24h) from the day of the donors pick up until 8 week of pregnancy
arm group label: ALA + P
arm group label: P
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 50 Years
healthy volunteers: No
facility: 
country: Greece
citation: Monastra G, De Grazia S, Cilaker Micili S, Goker A, Unfer V. Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage. Expert Opin Drug Deliv. 2016 Dec;13(12):1695-1708. doi: 10.1080/17425247.2016.1200556. Epub 2016 Jun 24.
PMID: 27292272
citation: Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012 Dec;18(12):1754-67. doi: 10.1038/nm.3012.
PMID: 23223073
responsible party type: Sponsor
mesh term: Infertility
mesh term: Thioctic Acid
mesh term: Progesterone