<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/NCT04413994</url>
  </required_header>
  <id_info>
    <org_study_id>NEOVASC</org_study_id>
    <secondary_id>868624</secondary_id>
    <nct_id>NCT04413994</nct_id>
  </id_info>
  <brief_title>Exclusive Human-milk in Preterm NEOnates and Early VASCular Aging Risk Factors (NEOVASC)</brief_title>
  <acronym>NEOVASC</acronym>
  <official_title>Effects of an Exclusive Human-milk Diet in Preterm NEOnates on Early VASCular Aging Risk Factors (NEOVASC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prolacta Bioscience</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Federal University Teaching Hospital, Feldkirch, Austria</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Paracelsus Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Prolacta Bioscience</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>
      Early vascular aging has its origins in fetal and neonatal life. The NEOVASC clinical trial&#xD;
      aims to determine the effects of an exclusive human milk diet in extremely preterm infants on&#xD;
      long-term cardiovascular health.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Early vascular aging has its origins in fetal and neonatal life. This early period of life&#xD;
      plays an important role in the development of obesity, high blood pressure, abnormalities in&#xD;
      lipid metabolism and non-insulin dependent diabetes. Increased cardiovascular risk in&#xD;
      formerly preterm infants constitutes a health problem of steadily growing relevance. Emerging&#xD;
      evidence suggests that human milk feeding has substantial benefits to the health of all&#xD;
      infants, especially for those born prematurely. Unfortunately, human milk alone does not&#xD;
      provide sufficient concentrations of nutrients, especially calcium, phosphorus, protein, and&#xD;
      fat needed for these infants to grow satisfactorily. For that purpose, fortifiers are used to&#xD;
      help increase the nutritional value of human milk.&#xD;
&#xD;
      The NEOVASC study is a multicentric, prospective, randomized, controlled, open and parallel&#xD;
      group clinical trial. A total of 200 extremely preterm infants and 100 term infants are&#xD;
      recruited for the test and control group, respectively. Infants in the test group (i.e.,&#xD;
      premature neonates) are randomized to either:&#xD;
&#xD;
        1. An exclusive human milk diet which contains mother's milk or pasteurized donor human&#xD;
           milk and a human milk fortifier until 36 weeks of gestation; OR&#xD;
&#xD;
        2. Human milk (as long as available) and a human milk fortifier (as long as human milk is&#xD;
           available) until a maximum of 32 weeks of gestation and thereafter human milk with a&#xD;
           bovine-based fortifier or preterm formula.&#xD;
&#xD;
      After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is&#xD;
      used in both groups. As a control group, term-born age-matched controls are included.&#xD;
      Participants within this control group are not enrolled at the time of birth but instead&#xD;
      recruited in various kindergartens at the age of five. Therefore, data from birth is taken&#xD;
      from the mother-child-booklet, which contains clinical records about the pregnancy, birth and&#xD;
      early life of children born in Austria. The total study duration is scheduled for 96 months&#xD;
      with a recruitment phase of 36 months. Follow-up visits are planned at one, two and five&#xD;
      years of age for the test group.&#xD;
&#xD;
      The purpose of the NEOVASC clinical trial is to characterize early life stressors by&#xD;
      assessing the effects of a physiological (i.e., human milk-based) nutrition in extremely&#xD;
      preterm infants during the vulnerable preterm period on the risk of metabolic and vascular&#xD;
      complications in later life. Outcomes include predictors and intermediate components of&#xD;
      cardiovascular disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 9, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2028</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2028</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>
    <intervention_model_description>The NEO-VASC study is a multicentric, prospective, randomized, controlled, open and parallel group clinical trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fasting blood glucose</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;five years&quot;</time_frame>
    <description>Primary outcome is the difference in fasting blood glucose at five years of age</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;five years&quot;</time_frame>
    <description>Primary outcome is the difference in blood pressure at five years of age</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Distensibility of aorta</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;five years&quot;</time_frame>
    <description>Primary outcome is the difference in the distensibility of the descending aorta using validated echocardiographic protocols at five years of age</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fasting blood glucose</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;24 months&quot;</time_frame>
    <description>Secondary outcome is fasting glucose at a corrected age of one and two years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;24 months&quot;</time_frame>
    <description>Secondary outcome is blood pressure at a corrected age of one and two years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;five years&quot;</time_frame>
    <description>Secondary outcome is BMI at five years of age, weight in kilograms and height in meters will be combined to report BMI in kg/m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;five years&quot;</time_frame>
    <description>Secondary outcome is insulin sensitivity at five years of age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>&quot;First day of life&quot; up to &quot;five years&quot;</time_frame>
    <description>Secondary outcome is lipid profile at five years of age</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fasting blood glucose</measure>
    <time_frame>&quot;five years of age&quot;</time_frame>
    <description>Difference in fasting blood glucose between preterm- and term-born children at five years of age</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>&quot;five years of age&quot;</time_frame>
    <description>Difference in blood pressure between preterm- and term-born children at five years of age</description>
  </other_outcome>
  <other_outcome>
    <measure>Distensibility of the descending aorta</measure>
    <time_frame>&quot;five years of age&quot;</time_frame>
    <description>Difference in the distensibility of the descending aorta between preterm- and term-born children using validated echocardiographic protocols at five years of age Results will be compared to results of term-born children</description>
  </other_outcome>
  <other_outcome>
    <measure>BMI</measure>
    <time_frame>&quot;five years of age&quot;</time_frame>
    <description>Difference in BMI between preterm- and term-born children at five years of age, weight in kilograms and height in meters will be combined to report BMI in kg/m2</description>
  </other_outcome>
  <other_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>&quot;five years of age&quot;</time_frame>
    <description>Difference in insulin sensitivity between preterm- and term-born children at five years of age</description>
  </other_outcome>
  <other_outcome>
    <measure>Lipid profile</measure>
    <time_frame>&quot;five years of age&quot;</time_frame>
    <description>Difference in lipid profile between preterm- and term-born children at five years of age</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Prematurity</condition>
  <condition>Vascular Aging</condition>
  <arm_group>
    <arm_group_label>Randomized study product group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>receiving study product (human milk fortifier &quot;Humavant&quot;) until a gestational age of 36 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>receiving study product until a gestational age of 32 weeks and reference product (bovine based fortifier or bovine formula) after 32 weeks of gestation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Term control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Term-born controls as a reference group for outcome parameters</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Humavant</intervention_name>
    <description>Premature infants are randomized to either:&#xD;
An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and the human milk fortifier until 36 weeks of gestation; OR&#xD;
Human milk (as long as available) and the human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula.&#xD;
After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included.</description>
    <arm_group_label>Randomized control group</arm_group_label>
    <arm_group_label>Randomized study product group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Preterm-born group:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Extremely preterm infants with a birth weight of 500-1250g.&#xD;
&#xD;
          2. Feeding is NPO or exclusive human milk prior to enrollment.&#xD;
&#xD;
          3. Parent(s) willing to sign informed consent.-&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Infants with a birth weight &lt;500g or &gt;1250g&#xD;
&#xD;
          2. Subjects diagnosed with inborn errors of metabolism such as galactosemia,&#xD;
             phenylketonuria&#xD;
&#xD;
          3. Subjects who have not been NPO or fed exclusive human milk diet prior to enrollment.&#xD;
&#xD;
          4. Presence of major congenital malformation.&#xD;
&#xD;
          5. Presence of intestinal perforation or Stage 2 Necrotizing enterocolitis prior to&#xD;
             enrollment.&#xD;
&#xD;
          6. Parent(s) not willing to sign informed consent.&#xD;
&#xD;
          7. Unable to participate for any reason based on the decision of the study investigator&#xD;
             (e.g. unlikely to survive the study period).&#xD;
&#xD;
        Term-born group:&#xD;
&#xD;
        Inclusion criteria&#xD;
&#xD;
          1. Term-born children with an adequate birth weight&#xD;
&#xD;
          2. Parent(s) willing to sign informed consent&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Subjects with acute or chronic illness&#xD;
&#xD;
          2. Parent(s) not willing to sign informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>5 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ursula Kiechl-Kohlendorfer, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Innsbruck</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ursula Kiechl-Kohlendorfer, MD, MSc</last_name>
    <phone>+43 512 504 27309</phone>
    <email>ursula.kohlendorfer@i-med.ac.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wolfgang Mitterer, MD</last_name>
    <phone>+43 670 2021490</phone>
    <email>wolfgang.mitterer@student.i-med.ac.at</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medical University of Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <state>Tyrol</state>
        <zip>A-6020</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ursula Kiechl-Kohlendorfer, MD, MSc</last_name>
      <phone>+43 512 504 27309</phone>
      <email>ursula.kohlendorfer@i-med.ac.at</email>
    </contact>
    <contact_backup>
      <last_name>Wolfgang Mitterer, MD</last_name>
      <email>wolfgang.mitterer@student.i-med.ac.at</email>
    </contact_backup>
    <investigator>
      <last_name>Christoph Binder, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Martin Wald, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Burkhard Simma, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>October 2, 2022</last_update_submitted>
  <last_update_submitted_qc>October 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University Innsbruck</investigator_affiliation>
    <investigator_full_name>Ursula Kohlendorfer</investigator_full_name>
    <investigator_title>Professor</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>
  <patient_data>
    <sharing_ipd>No</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/NCT04413994
org study id: NEOVASC
secondary id: 868624
nct id: NCT04413994
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Early vascular aging has its origins in fetal and neonatal life. The NEOVASC clinical trial
      aims to determine the effects of an exclusive human milk diet in extremely preterm infants on
      long-term cardiovascular health.
Early vascular aging has its origins in fetal and neonatal life. This early period of life
      plays an important role in the development of obesity, high blood pressure, abnormalities in
      lipid metabolism and non-insulin dependent diabetes. Increased cardiovascular risk in
      formerly preterm infants constitutes a health problem of steadily growing relevance. Emerging
      evidence suggests that human milk feeding has substantial benefits to the health of all
      infants, especially for those born prematurely. Unfortunately, human milk alone does not
      provide sufficient concentrations of nutrients, especially calcium, phosphorus, protein, and
      fat needed for these infants to grow satisfactorily. For that purpose, fortifiers are used to
      help increase the nutritional value of human milk.

      The NEOVASC study is a multicentric, prospective, randomized, controlled, open and parallel
      group clinical trial. A total of 200 extremely preterm infants and 100 term infants are
      recruited for the test and control group, respectively. Infants in the test group (i.e.,
      premature neonates) are randomized to either:

        1. An exclusive human milk diet which contains mother's milk or pasteurized donor human
           milk and a human milk fortifier until 36 weeks of gestation; OR

        2. Human milk (as long as available) and a human milk fortifier (as long as human milk is
           available) until a maximum of 32 weeks of gestation and thereafter human milk with a
           bovine-based fortifier or preterm formula.

      After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is
      used in both groups. As a control group, term-born age-matched controls are included.
      Participants within this control group are not enrolled at the time of birth but instead
      recruited in various kindergartens at the age of five. Therefore, data from birth is taken
      from the mother-child-booklet, which contains clinical records about the pregnancy, birth and
      early life of children born in Austria. The total study duration is scheduled for 96 months
      with a recruitment phase of 36 months. Follow-up visits are planned at one, two and five
      years of age for the test group.

      The purpose of the NEOVASC clinical trial is to characterize early life stressors by
      assessing the effects of a physiological (i.e., human milk-based) nutrition in extremely
      preterm infants during the vulnerable preterm period on the risk of metabolic and vascular
      complications in later life. Outcomes include predictors and intermediate components of
      cardiovascular disease.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The NEO-VASC study is a multicentric, prospective, randomized, controlled, open and parallel group clinical trial.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Fasting blood glucose
time frame: "First day of life" up to "five years"
description: Primary outcome is the difference in fasting blood glucose at five years of age
measure: Blood pressure
time frame: "First day of life" up to "five years"
description: Primary outcome is the difference in blood pressure at five years of age
measure: Distensibility of aorta
time frame: "First day of life" up to "five years"
description: Primary outcome is the difference in the distensibility of the descending aorta using validated echocardiographic protocols at five years of age
measure: Fasting blood glucose
time frame: "First day of life" up to "24 months"
description: Secondary outcome is fasting glucose at a corrected age of one and two years.
measure: Blood pressure
time frame: "First day of life" up to "24 months"
description: Secondary outcome is blood pressure at a corrected age of one and two years.
measure: BMI
time frame: "First day of life" up to "five years"
description: Secondary outcome is BMI at five years of age, weight in kilograms and height in meters will be combined to report BMI in kg/m2
measure: Insulin sensitivity
time frame: "First day of life" up to "five years"
description: Secondary outcome is insulin sensitivity at five years of age
measure: Lipid profile
time frame: "First day of life" up to "five years"
description: Secondary outcome is lipid profile at five years of age
measure: Fasting blood glucose
time frame: "five years of age"
description: Difference in fasting blood glucose between preterm- and term-born children at five years of age
measure: Blood pressure
time frame: "five years of age"
description: Difference in blood pressure between preterm- and term-born children at five years of age
measure: Distensibility of the descending aorta
time frame: "five years of age"
description: Difference in the distensibility of the descending aorta between preterm- and term-born children using validated echocardiographic protocols at five years of age Results will be compared to results of term-born children
measure: BMI
time frame: "five years of age"
description: Difference in BMI between preterm- and term-born children at five years of age, weight in kilograms and height in meters will be combined to report BMI in kg/m2
measure: Insulin sensitivity
time frame: "five years of age"
description: Difference in insulin sensitivity between preterm- and term-born children at five years of age
measure: Lipid profile
time frame: "five years of age"
description: Difference in lipid profile between preterm- and term-born children at five years of age
arm group label: Randomized study product group
arm group type: Active Comparator
description: receiving study product (human milk fortifier "Humavant") until a gestational age of 36 weeks
arm group label: Randomized control group
arm group type: Active Comparator
description: receiving study product until a gestational age of 32 weeks and reference product (bovine based fortifier or bovine formula) after 32 weeks of gestation
arm group label: Term control group
arm group type: No Intervention
description: Term-born controls as a reference group for outcome parameters
intervention type: Dietary Supplement
intervention name: Humavant
description: Premature infants are randomized to either:
An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and the human milk fortifier until 36 weeks of gestation; OR
Human milk (as long as available) and the human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula.
After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included.
arm group label: Randomized control group
arm group label: Randomized study product group
criteria: 
gender: All
minimum age: 1 Day
maximum age: 5 Years
healthy volunteers: No
last name: Ursula Kiechl-Kohlendorfer, MD, MSc
role: Principal Investigator
affiliation: Medical University of Innsbruck
last name: Ursula Kiechl-Kohlendorfer, MD, MSc
phone: +43 512 504 27309
email: ursula.kohlendorfer@i-med.ac.at
last name: Wolfgang Mitterer, MD
phone: +43 670 2021490
email: wolfgang.mitterer@student.i-med.ac.at
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University Innsbruck
investigator full name: Ursula Kohlendorfer
investigator title: Professor
mesh term: Premature Birth
sharing ipd: No