xml: <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/NCT06015828</url>
    </required_header>
    <id_info>
      <org_study_id>AinShamsUlactoferrin</org_study_id>
      <nct_id>NCT06015828</nct_id>
    </id_info>
    <brief_title>Effect of Enteral Bovine Lactoferrin in Preterm Infants</brief_title>
    <official_title>Effect of Enteral Bovine Lactoferrin on Neurobehavioral Performance of Preterm Infants</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ain Shams University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Ain Shams University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        There is a preference for using enteral bovine lactoferrin for preterm infants. Lactoferrin&#xD;
        is a sialic acid-rich, iron-binding milk glycoprotein, known to have multifunctional health&#xD;
        beneﬁts, including its ability to modulate immune function and facilitate iron absorption, as&#xD;
        well as its antibacterial and anti inﬂammatory actions.&#xD;
  &#xD;
        The study is an evaluation of the efficacy of enteral bovine lactoferrin on neurobehavioral&#xD;
        performance in preterm infants.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Over 15 million infants are born preterm &lt; 37 weeks gestation worldwide. (World Health&#xD;
        Organization et al., 2015).&#xD;
  &#xD;
        Lactoferrin is about 80- kilo dalton kDa glycoprotein composed of 703 amino acid residues and&#xD;
        is a member of the transferrin family, As a member of the transferrin family of iron-binding&#xD;
        proteins, lactoferrin shares more than 60% homology at the amino acid level with transferrin&#xD;
        and a 77% homology exists between human and bovine species. (Karav et al., 2018).&#xD;
  &#xD;
        Human lactoferrin is the most abundant glycoprotein. It contains 1- 4 Sialic acid residues at&#xD;
        the terminal position of N-linked glycan chains for each lactoferrin molecule. (Lonnerdal et&#xD;
        al., 2011).&#xD;
  &#xD;
        Poly Sialic acid plays a critical role in neural development by modulating the adhesive&#xD;
        property of neural cell adhesion molecule and is, therefore, implicated in a wide range of&#xD;
        morphogenic events, including cell migration, neuronal outgrowth, path-ﬁnding, sprouting,&#xD;
        regeneration, synaptic plasticity, and serving a &quot;reservoir function&quot; for neurotrophic&#xD;
        factors. Sia, a key monomeric building block of poly Sialic acid, plays crucial roles in&#xD;
        cell-to-cell interactions, neuronal outgrowth, modifying synaptic connectivity, and memory&#xD;
        formation (Wang et al., 2012).&#xD;
  &#xD;
        An important functional property of lactoferrin is its high afﬁnity for binding iron (Kumar&#xD;
        et al.,2013).&#xD;
  &#xD;
        Iron is a ubiquitous metal that is essential for the function of all mammalian cells. Iron&#xD;
        deﬁciency affects neuronal metabolism, neurotransmitter function, and myelination, which have&#xD;
        the greatest impact on the brain during early neurodevelopment (Cheli et al., 2018).&#xD;
  &#xD;
        Lactoferrin is unique in that it contains 2 nutritional molecules of iron and Sialic acid,&#xD;
        which are key components involved in early neurodevelopmental and cognitive function for&#xD;
        infants (Chen et al.,2015).&#xD;
  &#xD;
        Lactoferrin is a bifidogenic glycoprotein found in all vertebrates and mammalian milk,&#xD;
        leukocytes, and exocrine secretions (Chahine et al.,2012).&#xD;
  &#xD;
        Inﬂammation has an adverse impact on cognition, and IL-1β, IL-6, and tumor necrosis factor&#xD;
        alpha TNF-α are closely associated with long-term potentiation (LTP) and synaptic plasticity&#xD;
        (Özkorumak et al., 2019).&#xD;
  &#xD;
        Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying (Ochoa et al.,&#xD;
        2019).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">September 20, 2021</start_date>
    <completion_date type="Actual">April 20, 2023</completion_date>
    <primary_completion_date type="Actual">September 20, 2022</primary_completion_date>
    <phase>N/A</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>Supportive Care</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Double-blinded randomized controlled trial Neonates will be randomized using closed envelopes into two groups</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>neurobehavioral outcome</measure>
      <time_frame>at 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer.</time_frame>
      <description>The present study is designed to evaluate the effect of oral administration of bovine lactoferrin on the neurobehavioral performance of preterm neonates at 36 weeks corrected age using the Neonatal Intensive Care Unit Neurobehavioral Scale (NNNS).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Morbidity</measure>
      <time_frame>At 36 weeks corrected gestational age</time_frame>
      <description>Define any morbidities from oral lactoferrn administration</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mortality</measure>
      <time_frame>36 corrected gestational age</time_frame>
      <description>To assess number of deaths in the study group</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>effect on morbidity and mortality</measure>
      <time_frame>at 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer.</time_frame>
      <description>effect on mortality and major morbidity at 36 weeks corrected gestational age defined as periventricular leukomalacia, necrotizing enterocolitis, and late-onset sepsis.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">80</enrollment>
    <condition>to Evaluate the Effect of Oral Administration of Bovine Lactoferrin on the Neurobehavioral Performance of Preterm Neonates</condition>
    <arm_group>
      <arm_group_label>lactoferrin group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Neonates will receive a daily dose of 150 mg/kg body weight per day (up to a maximum of 300 mg/day) of bovine lactoferrin and will be prepared for administration by addition by syringe of sterile water (4 mL) orally or through gavage feeding, once the infant's enteral feed volume is more than 12 mL/kg per day until 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer. (Asztalos.,et al 2020)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>control group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Neonates will receive their routine feds and will not receive lactoferrin.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>bovine lactoferrin</intervention_name>
      <description>Neonates will receive a daily dose of 150 mg/kg body weight per day (up to a maximum of 300 mg/day) of bovine lactoferrin and will be prepared for administration by addition by syringe of sterile water (4 mL) orally or through gavage feeding, once the infant's enteral feed volume is more than 12 mL/kg per day until 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer.</description>
      <arm_group_label>lactoferrin group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Stable preterm neonates&#xD;
  &#xD;
            -  gestational age less than 35 weeks&#xD;
  &#xD;
            -  younger than 72 hours at randomization&#xD;
  &#xD;
            -  have initiated enteral feds.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1. Neonates with underlying gastrointestinal problems that prevent oral intake. 2.&#xD;
               Neonates with predisposing conditions that profoundly affect growth and development&#xD;
               (chromosomal abnormalities,&#xD;
  &#xD;
            -  structural brain anomalies,&#xD;
  &#xD;
            -  severe congenital abnormalities). 3. Neonates with a history of perinatal hypoxia. 4.&#xD;
               Neonates with a family background of cow milk allergy. 5. Evidence of feeding&#xD;
               difficulties or formula intolerance, such as vomiting or poor intake.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Hour</minimum_age>
      <maximum_age>3 Days</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>maha mohamed, PHD</last_name>
      <role>Study Director</role>
      <affiliation>Ain Shams University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>dina shinkar, PHD</last_name>
      <role>Study Director</role>
      <affiliation>Ain Shams University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>mariam ibrahim, PHD</last_name>
      <role>Study Director</role>
      <affiliation>Ain Shams University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>mahmoud kofory, MB.,B.CH</last_name>
      <role>Principal Investigator</role>
      <affiliation>Azhar University</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Ain Shams University Hospitals</name>
        <address>
          <city>Cairo</city>
          <state>Al Qahirah</state>
          <zip>1825</zip>
          <country>Egypt</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Egypt</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Ain Shams University</investigator_affiliation>
      <investigator_full_name>Mariam Ibrahim</investigator_full_name>
      <investigator_title>assistant professor of pediatrics, Ian shams university</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Premature Birth</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lactoferrin</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06015828
  org study id: AinShamsUlactoferrin
  nct id: NCT06015828
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  There is a preference for using enteral bovine lactoferrin for preterm infants. Lactoferrin
        is a sialic acid-rich, iron-binding milk glycoprotein, known to have multifunctional health
        beneﬁts, including its ability to modulate immune function and facilitate iron absorption, as
        well as its antibacterial and anti inﬂammatory actions.
  
        The study is an evaluation of the efficacy of enteral bovine lactoferrin on neurobehavioral
        performance in preterm infants.
  Over 15 million infants are born preterm < 37 weeks gestation worldwide. (World Health
        Organization et al., 2015).
  
        Lactoferrin is about 80- kilo dalton kDa glycoprotein composed of 703 amino acid residues and
        is a member of the transferrin family, As a member of the transferrin family of iron-binding
        proteins, lactoferrin shares more than 60% homology at the amino acid level with transferrin
        and a 77% homology exists between human and bovine species. (Karav et al., 2018).
  
        Human lactoferrin is the most abundant glycoprotein. It contains 1- 4 Sialic acid residues at
        the terminal position of N-linked glycan chains for each lactoferrin molecule. (Lonnerdal et
        al., 2011).
  
        Poly Sialic acid plays a critical role in neural development by modulating the adhesive
        property of neural cell adhesion molecule and is, therefore, implicated in a wide range of
        morphogenic events, including cell migration, neuronal outgrowth, path-ﬁnding, sprouting,
        regeneration, synaptic plasticity, and serving a "reservoir function" for neurotrophic
        factors. Sia, a key monomeric building block of poly Sialic acid, plays crucial roles in
        cell-to-cell interactions, neuronal outgrowth, modifying synaptic connectivity, and memory
        formation (Wang et al., 2012).
  
        An important functional property of lactoferrin is its high afﬁnity for binding iron (Kumar
        et al.,2013).
  
        Iron is a ubiquitous metal that is essential for the function of all mammalian cells. Iron
        deﬁciency affects neuronal metabolism, neurotransmitter function, and myelination, which have
        the greatest impact on the brain during early neurodevelopment (Cheli et al., 2018).
  
        Lactoferrin is unique in that it contains 2 nutritional molecules of iron and Sialic acid,
        which are key components involved in early neurodevelopmental and cognitive function for
        infants (Chen et al.,2015).
  
        Lactoferrin is a bifidogenic glycoprotein found in all vertebrates and mammalian milk,
        leukocytes, and exocrine secretions (Chahine et al.,2012).
  
        Inﬂammation has an adverse impact on cognition, and IL-1β, IL-6, and tumor necrosis factor
        alpha TNF-α are closely associated with long-term potentiation (LTP) and synaptic plasticity
        (Özkorumak et al., 2019).
  
        Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying (Ochoa et al.,
        2019).
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Supportive Care
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Double-blinded randomized controlled trial Neonates will be randomized using closed envelopes into two groups
  measure: neurobehavioral outcome
  time frame: at 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer.
  description: The present study is designed to evaluate the effect of oral administration of bovine lactoferrin on the neurobehavioral performance of preterm neonates at 36 weeks corrected age using the Neonatal Intensive Care Unit Neurobehavioral Scale (NNNS).
  measure: Morbidity
  time frame: At 36 weeks corrected gestational age
  description: Define any morbidities from oral lactoferrn administration
  measure: Mortality
  time frame: 36 corrected gestational age
  description: To assess number of deaths in the study group
  measure: effect on morbidity and mortality
  time frame: at 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer.
  description: effect on mortality and major morbidity at 36 weeks corrected gestational age defined as periventricular leukomalacia, necrotizing enterocolitis, and late-onset sepsis.
  arm group label: lactoferrin group
  arm group type: Experimental
  description: Neonates will receive a daily dose of 150 mg/kg body weight per day (up to a maximum of 300 mg/day) of bovine lactoferrin and will be prepared for administration by addition by syringe of sterile water (4 mL) orally or through gavage feeding, once the infant's enteral feed volume is more than 12 mL/kg per day until 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer. (Asztalos.,et al 2020)
  arm group label: control group
  arm group type: No Intervention
  description: Neonates will receive their routine feds and will not receive lactoferrin.
  intervention type: Dietary Supplement
  intervention name: bovine lactoferrin
  description: Neonates will receive a daily dose of 150 mg/kg body weight per day (up to a maximum of 300 mg/day) of bovine lactoferrin and will be prepared for administration by addition by syringe of sterile water (4 mL) orally or through gavage feeding, once the infant's enteral feed volume is more than 12 mL/kg per day until 36 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer.
  arm group label: lactoferrin group
  criteria: 
  gender: All
  minimum age: 1 Hour
  maximum age: 3 Days
  healthy volunteers: Accepts Healthy Volunteers
  last name: maha mohamed, PHD
  role: Study Director
  affiliation: Ain Shams University
  last name: dina shinkar, PHD
  role: Study Director
  affiliation: Ain Shams University
  last name: mariam ibrahim, PHD
  role: Study Director
  affiliation: Ain Shams University
  last name: mahmoud kofory, MB.,B.CH
  role: Principal Investigator
  affiliation: Azhar University
  facility: 
  country: Egypt
  responsible party type: Principal Investigator
  investigator affiliation: Ain Shams University
  investigator full name: Mariam Ibrahim
  investigator title: assistant professor of pediatrics, Ian shams university
  mesh term: Premature Birth
  mesh term: Lactoferrin