<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/NCT01695070</url>
  </required_header>
  <id_info>
    <org_study_id>U1111-1133-4541</org_study_id>
    <secondary_id>ACTRN12612000858897</secondary_id>
    <nct_id>NCT01695070</nct_id>
  </id_info>
  <brief_title>Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies</brief_title>
  <official_title>A Pilot Study of Maternally Administered Melatonin to Decrease the Level of Oxidative Stress in Human Pregnancies Affected by Intrauterine Growth Restriction.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Monash University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Monash University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intrauterine growth restriction is the term used to describe a condition where an unborn baby&#xD;
      does not reach its optimum size. In the short and long term, intrauterine growth restricted&#xD;
      babies have a higher risk of serious disease and even death. It is well established that very&#xD;
      low levels of oxygen in the baby's blood can harm the baby's health through a state known as&#xD;
      oxidative stress. Currently, there is no established treatment available to treat&#xD;
      intrauterine growth restriction or its complications. In experimental animal studies however,&#xD;
      the naturally occuring hormone, melatonin, has been shown to significantly reduce oxidative&#xD;
      stress and improve health of the unborn babies that have suffered from intrauterine growth&#xD;
      restriction. This study aims to find out if the use melatonin twice per day throughout&#xD;
      pregnancies affected by intrauterine growth restriction will lower the level of oxidative&#xD;
      stress experienced by the unborn baby. If this is the case melatonin may help protect the&#xD;
      unborn baby from damage caused by oxidative stress, this will be studied in a separate future&#xD;
      study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</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>Oxidative stress in the umbilical artery</measure>
    <time_frame>Once, at birth.</time_frame>
    <description>Umbilical artery oxidative stress by measuring levels of malondialdehyde (MDA) and 8-isoprostane. Levels of MDA will be assessed using a Thiobarbituric Acid Reactive Substances Assay Kit (Cayman Chemical Item Number 10009055). Levels of 8-isoprostane will be assessed using an 8-Isoprostane Enzyme Immuno Assay Kit (Cayman Chemical Item Number 516351).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oxidative stress in maternal venous serum</measure>
    <time_frame>Once within one week before start treatment and once per week during the treatment period (estimated to be an average of 4 weeks).</time_frame>
    <description>Maternal serum oxidative stress will be assessed by measuring levels of malondialdehyde (MDA) and 8-isoprostane. Levels of MDA will be assessed using a Thiobarbituric Acid Reactive Substances Assay Kit (Cayman Chemical Item Number 10009055). Levels of 8-isoprostane will be assessed using an 8-Isoprostane Enzyme Immuno Assay Kit (Cayman Chemical Item Number 516351).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetoplacental Doppler studies</measure>
    <time_frame>Once within one week before start treatment and twice per week during the treatment period (estimated to be an average of 4 weeks).</time_frame>
    <description>Fetoplacental Doppler studies (umbilical artery, uterine artery, middle cerebral artery, ductus venosus). Fetoplacental Doppler studies are performed in the clinical assessment of women diagnosed with intrauterine growth restriction by sonography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placental oxidative stress</measure>
    <time_frame>Once, at birth.</time_frame>
    <description>Placental oxidative stress is assessed by measuring levels of malondialdehyde (MDA) and 8-isoprostane. Levels of MDA will be assessed using a Thiobarbituric Acid Reactive Substances Assay Kit (Cayman Chemical Item Number 10009055). Levels of 8-isoprostane will be assessed using an 8-Isoprostane Enzyme Immuno Assay Kit (Cayman Chemical Item Number 516351)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gestational age at birth.</measure>
    <time_frame>Once, at birth.</time_frame>
    <description>Gestational age at birth will be calculated using the last menstrual period and ultrasound characteristics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite neonatal outcome.</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, up to 12 months.</time_frame>
    <description>Composite neonatal outcome (admission to NICU, duration of admission, need and duration of respiratory support, intraventricular haemorrhage, necrotising enterocolitis, abnormal neurological assessment, mortality before discharge). This composite neonatal outcome will be measured by collecting medical record data after clinical assessments.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Fetal Growth Retardation</condition>
  <arm_group>
    <arm_group_label>Melatonin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women with IUGR will take 4mg prolonged release melatonin oral tablets twice daily. Treatment will occur as soon as the diagnosis of intrauterine growth restriction is made and the patient has been enrolled to this study until birth. The overall duration of treatment will vary due to the nature of intrauterine growth restriction.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <description>4mg prolonged release melatonin oral tablets twice daily</description>
    <arm_group_label>Melatonin</arm_group_label>
    <other_name>Circadin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Estimated fetal weight &lt;10th percentile in combination with abnormal fetoplacental&#xD;
             Doppler studies.&#xD;
&#xD;
          -  Singleton pregnancy.&#xD;
&#xD;
          -  Live fetus.&#xD;
&#xD;
          -  Gestational age: from 23+0 weeks until 34+0 weeks.&#xD;
&#xD;
          -  Normal fetal anatomy on ultrasound.&#xD;
&#xD;
          -  Confirmed gestational age.&#xD;
&#xD;
          -  No indication for immediate delivery.&#xD;
&#xD;
          -  Basic understanding of the English language.&#xD;
&#xD;
          -  18 years or older.&#xD;
&#xD;
          -  Consent obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fetal demise.&#xD;
&#xD;
          -  Multiple pregnancy.&#xD;
&#xD;
          -  Known abnormal karyotype.&#xD;
&#xD;
          -  Presence of any congenital abnormality.&#xD;
&#xD;
          -  Unknown duration of pregnancy.&#xD;
&#xD;
          -  IUGR attributable to non-placental factors.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicole O Alers, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Ritchie Centre, Monash Institute of Medical Research, Monash University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Euan M Wallace, MBChB MD FRCOG FRANZCOG</last_name>
    <role>Principal Investigator</role>
    <affiliation>Southern Health, The Ritchie Centre, Monash Institute of Medical Research, Monash University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Graham Jenkin, BSc PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Ritchie Centre, Monash Institute of Medical Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Suzanne L Miller, BSc PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Ritchie Centre, Monash Institute of Medical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Southern Health: Monash Medical Centre and Jessie McPherson Private Hospital</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>November 14, 2014</last_update_submitted>
  <last_update_submitted_qc>November 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 18, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Monash University</investigator_affiliation>
    <investigator_full_name>Nicole Alers</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fetal Growth Retardation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</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/NCT01695070
org study id: U1111-1133-4541
secondary id: ACTRN12612000858897
nct id: NCT01695070
lead sponsor: 
has dmc: No
Intrauterine growth restriction is the term used to describe a condition where an unborn baby
      does not reach its optimum size. In the short and long term, intrauterine growth restricted
      babies have a higher risk of serious disease and even death. It is well established that very
      low levels of oxygen in the baby's blood can harm the baby's health through a state known as
      oxidative stress. Currently, there is no established treatment available to treat
      intrauterine growth restriction or its complications. In experimental animal studies however,
      the naturally occuring hormone, melatonin, has been shown to significantly reduce oxidative
      stress and improve health of the unborn babies that have suffered from intrauterine growth
      restriction. This study aims to find out if the use melatonin twice per day throughout
      pregnancies affected by intrauterine growth restriction will lower the level of oxidative
      stress experienced by the unborn baby. If this is the case melatonin may help protect the
      unborn baby from damage caused by oxidative stress, this will be studied in a separate future
      study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Oxidative stress in the umbilical artery
time frame: Once, at birth.
description: Umbilical artery oxidative stress by measuring levels of malondialdehyde (MDA) and 8-isoprostane. Levels of MDA will be assessed using a Thiobarbituric Acid Reactive Substances Assay Kit (Cayman Chemical Item Number 10009055). Levels of 8-isoprostane will be assessed using an 8-Isoprostane Enzyme Immuno Assay Kit (Cayman Chemical Item Number 516351).
measure: Oxidative stress in maternal venous serum
time frame: Once within one week before start treatment and once per week during the treatment period (estimated to be an average of 4 weeks).
description: Maternal serum oxidative stress will be assessed by measuring levels of malondialdehyde (MDA) and 8-isoprostane. Levels of MDA will be assessed using a Thiobarbituric Acid Reactive Substances Assay Kit (Cayman Chemical Item Number 10009055). Levels of 8-isoprostane will be assessed using an 8-Isoprostane Enzyme Immuno Assay Kit (Cayman Chemical Item Number 516351).
measure: Fetoplacental Doppler studies
time frame: Once within one week before start treatment and twice per week during the treatment period (estimated to be an average of 4 weeks).
description: Fetoplacental Doppler studies (umbilical artery, uterine artery, middle cerebral artery, ductus venosus). Fetoplacental Doppler studies are performed in the clinical assessment of women diagnosed with intrauterine growth restriction by sonography.
measure: Placental oxidative stress
time frame: Once, at birth.
description: Placental oxidative stress is assessed by measuring levels of malondialdehyde (MDA) and 8-isoprostane. Levels of MDA will be assessed using a Thiobarbituric Acid Reactive Substances Assay Kit (Cayman Chemical Item Number 10009055). Levels of 8-isoprostane will be assessed using an 8-Isoprostane Enzyme Immuno Assay Kit (Cayman Chemical Item Number 516351)
measure: Gestational age at birth.
time frame: Once, at birth.
description: Gestational age at birth will be calculated using the last menstrual period and ultrasound characteristics.
measure: Composite neonatal outcome.
time frame: Participants will be followed for the duration of hospital stay, up to 12 months.
description: Composite neonatal outcome (admission to NICU, duration of admission, need and duration of respiratory support, intraventricular haemorrhage, necrotising enterocolitis, abnormal neurological assessment, mortality before discharge). This composite neonatal outcome will be measured by collecting medical record data after clinical assessments.
arm group label: Melatonin
arm group type: Experimental
description: Women with IUGR will take 4mg prolonged release melatonin oral tablets twice daily. Treatment will occur as soon as the diagnosis of intrauterine growth restriction is made and the patient has been enrolled to this study until birth. The overall duration of treatment will vary due to the nature of intrauterine growth restriction.
intervention type: Drug
intervention name: Melatonin
description: 4mg prolonged release melatonin oral tablets twice daily
arm group label: Melatonin
other name: Circadin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Nicole O Alers, MD
role: Principal Investigator
affiliation: The Ritchie Centre, Monash Institute of Medical Research, Monash University
last name: Euan M Wallace, MBChB MD FRCOG FRANZCOG
role: Principal Investigator
affiliation: Southern Health, The Ritchie Centre, Monash Institute of Medical Research, Monash University
last name: Graham Jenkin, BSc PhD
role: Principal Investigator
affiliation: The Ritchie Centre, Monash Institute of Medical Research
last name: Suzanne L Miller, BSc PhD
role: Principal Investigator
affiliation: The Ritchie Centre, Monash Institute of Medical Research
facility: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: Monash University
investigator full name: Nicole Alers
investigator title: MD
mesh term: Fetal Growth Retardation
mesh term: Melatonin