<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/NCT01686477</url>
  </required_header>
  <id_info>
    <org_study_id>CRO2006</org_study_id>
    <nct_id>NCT01686477</nct_id>
  </id_info>
  <brief_title>PREterM FOrmula Or Donor Breast Milk for Premature Babies</brief_title>
  <acronym>PREMFOOD</acronym>
  <official_title>Preterm Formula or Donor Breast Milk to Make up Any Shortfall in Mother's Own Milk</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In order to address this crucial question, central to preterm newborn care, a multicentre&#xD;
      United Kingdom (UK) -wide study randomising 4000 preterm babies would be necessary to achieve&#xD;
      sufficient power to evaluate the impact on the short-term outcomes necrotising enterocolitis&#xD;
      and bloodstream infection, and establish cohorts large enough to address long-term metabolic&#xD;
      (such as obesity, type 2 diabetes), cardiovascular (such as blood pressure) and developmental&#xD;
      outcomes. This pilot trial will evaluate the practicability and feasibility of such a large&#xD;
      multicentre UK randomised controlled trial. In addition to evaluating feasibility and to&#xD;
      ensure maximal use of resources allocated, this study will also assess outcomes that are&#xD;
      indicative of long term metabolic health.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mother's Own Milk (MOM) is recommended for preterm babies. However, on average, mothers&#xD;
      giving birth preterm are able to provide less than half their baby's milk requirements.&#xD;
      Standard clinical practice is to make up any shortfall in MOM with either pasteurised Human&#xD;
      Donor Milk (HDM) or Preterm Formula (PTF). Which option is more beneficial to clinical&#xD;
      outcomes is unknown.&#xD;
&#xD;
      Pasteurisation reduces or destroys many biologically active components and HDM, unlike PTF,&#xD;
      is very variable in composition. Clinicians who use HDM do so primarily in the hope that&#xD;
      despite pasteurisation it will reduce bloodstream infection and necrotising enterocolitis, a&#xD;
      serious, devastating inflammatory disease characterised by bowel death and multisystem&#xD;
      failure. These are two of the most feared conditions in newborn medicine as described above.&#xD;
      Landmark nutritional trials in the early 1980's suggest positive effects of human milk on&#xD;
      insulin sensitivity, and other metabolic outcomes. Clinicians who prefer PTF believe it&#xD;
      benefits growth, including brain growth, and improves neurodevelopmental outcome.&#xD;
&#xD;
      Neonates born below 32 weeks gestational age will be randomised to receive fortified HDM,&#xD;
      unfortified HDM, or PTF to make up any shortfall in MOM until 35 weeks postmenstrual age with&#xD;
      a sample size of 22 in each group. The trial is designed to reflect current preterm feeding&#xD;
      practice. The trial will take place in neonatal units in London and parent consent obtained&#xD;
      within 48hr of birth. Permission will be sought for long term follow up, initially from&#xD;
      parents (later from children themselves). Outcomes will be body composition using magnetic&#xD;
      resonance imaging and other imaging techniques. This pilot study will specifically assess&#xD;
      feasibility by testing 1) provision of HDM by Human Milk Banks in London 2) acceptability to&#xD;
      parents and clinicians using feedback on trial design 3) recruitment to target and 4)&#xD;
      retrieval of clinical data for all recruited babies form the National Neonatal Database.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2013</start_date>
  <completion_date type="Anticipated">January 15, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2019</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Body Adiposity</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
    <description>As measured by whole body Magnetic Resonance Imaging (MRI). The time taken to reach term age equivalent will vary depending on the birth gestational age of the infant. The range will be 8-15 weeks (representing gestational birth age from 25-32 weeks).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility data</measure>
    <time_frame>18 months</time_frame>
    <description>test the acceptability of the trial design with parents and clinicians&#xD;
test that recruitment to target is achievable, estimate consent and dropout rates&#xD;
estimate the trial requirement for HDM from National Health Service (NHS) Human Milk Banks&#xD;
test that clinical outcome data can be retrieved from operational NHS electronic records, thus minimising the burden of data capture and facilitating the use of linked NHS records to achieve long-term follow-up at low cost.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Total Body adiposity</measure>
    <time_frame>Term (37-42 weeks corrected gestational age) and 6 weeks corrected</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Regional adiposity, as measured by whole body MRI</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Non adipose tissue, as measured by whole body MRI</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Anthropometry (weight, length, and head circumference)</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Intra-hepatocellular Lipid, measured by magnetic resonance spectroscopy</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Stool and urine metabolomic profile, measured using high throughput nuclear magnetic resonance (NMR) spectroscopy</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Blood Quantitative Insulin Sensitivity Check Index (QUICKI)</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
    <description>Calculated from fasting pre feed blood glucose and insulin</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood microRNA profile using high throughput sequencing techniques</measure>
    <time_frame>Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Regional adiposity, as measured by whole body MRI</measure>
    <time_frame>Term plus 6 weeks corrected age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Non adipose tissue, as measured by whole body MRI</measure>
    <time_frame>Term plus 6 weeks corrected age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Anthropometry (weight, length, and head circumference)</measure>
    <time_frame>Term plus 6 weeks corrected age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Intra hepato-cellular Lipid, as measured by magnetic resonance spectroscopy</measure>
    <time_frame>Term plus 6 weeks corrected age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Term plus 6 weeks corrected</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Stool and urine metabolomic profile, measured using high throughput nuclear magnetic resonance (NMR) spectroscopy</measure>
    <time_frame>Term plus 6 weeks corrected</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">66</enrollment>
  <condition>Adiposity</condition>
  <condition>Insulin Resistance</condition>
  <condition>Metabolomic Profile</condition>
  <condition>microRNA Profile</condition>
  <arm_group>
    <arm_group_label>Unfortified Human Donor Milk</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Used to make up any shortfall in mother's own milk</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fortified Human Donor Milk</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Used to make up any shortfall in mother's own milk</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Preterm Formula</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Used to make up any shortfall in mother's own milk</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Unfortified Human donor Milk used to make up any shortfall in mother's own milk</intervention_name>
    <arm_group_label>Unfortified Human Donor Milk</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fortified Human donor Milk used to make up any shortfall in mother's own milk</intervention_name>
    <arm_group_label>Fortified Human Donor Milk</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Preterm Formula used when there is a shortfall in mother's own milk</intervention_name>
    <arm_group_label>Preterm Formula</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Preterm infants born between 25+0 to 31+6 weeks gestational age&#xD;
&#xD;
          -  Written informed consent from parents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Major congenital or life threatening abnormalities or congenital abnormalities that&#xD;
             preclude early milk feeding&#xD;
&#xD;
          -  Inability to randomise infant within 48 hours&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Weeks</minimum_age>
    <maximum_age>31 Weeks</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Neena Modi, MBChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chelsea and Westminster Hospital Neonatal Unit</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>June 27, 2019</last_update_submitted>
  <last_update_submitted_qc>June 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>September 30, 2021</submitted>
    <returned>October 28, 2021</returned>
    <submitted>September 29, 2022</submitted>
    <returned>August 18, 2023</returned>
  </pending_results>
  <!-- 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/NCT01686477
org study id: CRO2006
nct id: NCT01686477
lead sponsor: 
has dmc: No
In order to address this crucial question, central to preterm newborn care, a multicentre
      United Kingdom (UK) -wide study randomising 4000 preterm babies would be necessary to achieve
      sufficient power to evaluate the impact on the short-term outcomes necrotising enterocolitis
      and bloodstream infection, and establish cohorts large enough to address long-term metabolic
      (such as obesity, type 2 diabetes), cardiovascular (such as blood pressure) and developmental
      outcomes. This pilot trial will evaluate the practicability and feasibility of such a large
      multicentre UK randomised controlled trial. In addition to evaluating feasibility and to
      ensure maximal use of resources allocated, this study will also assess outcomes that are
      indicative of long term metabolic health.
Mother's Own Milk (MOM) is recommended for preterm babies. However, on average, mothers
      giving birth preterm are able to provide less than half their baby's milk requirements.
      Standard clinical practice is to make up any shortfall in MOM with either pasteurised Human
      Donor Milk (HDM) or Preterm Formula (PTF). Which option is more beneficial to clinical
      outcomes is unknown.

      Pasteurisation reduces or destroys many biologically active components and HDM, unlike PTF,
      is very variable in composition. Clinicians who use HDM do so primarily in the hope that
      despite pasteurisation it will reduce bloodstream infection and necrotising enterocolitis, a
      serious, devastating inflammatory disease characterised by bowel death and multisystem
      failure. These are two of the most feared conditions in newborn medicine as described above.
      Landmark nutritional trials in the early 1980's suggest positive effects of human milk on
      insulin sensitivity, and other metabolic outcomes. Clinicians who prefer PTF believe it
      benefits growth, including brain growth, and improves neurodevelopmental outcome.

      Neonates born below 32 weeks gestational age will be randomised to receive fortified HDM,
      unfortified HDM, or PTF to make up any shortfall in MOM until 35 weeks postmenstrual age with
      a sample size of 22 in each group. The trial is designed to reflect current preterm feeding
      practice. The trial will take place in neonatal units in London and parent consent obtained
      within 48hr of birth. Permission will be sought for long term follow up, initially from
      parents (later from children themselves). Outcomes will be body composition using magnetic
      resonance imaging and other imaging techniques. This pilot study will specifically assess
      feasibility by testing 1) provision of HDM by Human Milk Banks in London 2) acceptability to
      parents and clinicians using feedback on trial design 3) recruitment to target and 4)
      retrieval of clinical data for all recruited babies form the National Neonatal Database.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Total Body Adiposity
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
description: As measured by whole body Magnetic Resonance Imaging (MRI). The time taken to reach term age equivalent will vary depending on the birth gestational age of the infant. The range will be 8-15 weeks (representing gestational birth age from 25-32 weeks).
measure: Feasibility data
time frame: 18 months
description: test the acceptability of the trial design with parents and clinicians
test that recruitment to target is achievable, estimate consent and dropout rates
estimate the trial requirement for HDM from National Health Service (NHS) Human Milk Banks
test that clinical outcome data can be retrieved from operational NHS electronic records, thus minimising the burden of data capture and facilitating the use of linked NHS records to achieve long-term follow-up at low cost.
measure: Total Body adiposity
time frame: Term (37-42 weeks corrected gestational age) and 6 weeks corrected
measure: Regional adiposity, as measured by whole body MRI
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Non adipose tissue, as measured by whole body MRI
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Anthropometry (weight, length, and head circumference)
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Intra-hepatocellular Lipid, measured by magnetic resonance spectroscopy
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Blood pressure
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Stool and urine metabolomic profile, measured using high throughput nuclear magnetic resonance (NMR) spectroscopy
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Blood Quantitative Insulin Sensitivity Check Index (QUICKI)
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
description: Calculated from fasting pre feed blood glucose and insulin
measure: Blood microRNA profile using high throughput sequencing techniques
time frame: Measured as close as possible to the baby's due date, at an average age of 10 weeks (range 8 to 15 weeks)
measure: Regional adiposity, as measured by whole body MRI
time frame: Term plus 6 weeks corrected age
measure: Non adipose tissue, as measured by whole body MRI
time frame: Term plus 6 weeks corrected age
measure: Anthropometry (weight, length, and head circumference)
time frame: Term plus 6 weeks corrected age
measure: Intra hepato-cellular Lipid, as measured by magnetic resonance spectroscopy
time frame: Term plus 6 weeks corrected age
measure: Blood pressure
time frame: Term plus 6 weeks corrected
measure: Stool and urine metabolomic profile, measured using high throughput nuclear magnetic resonance (NMR) spectroscopy
time frame: Term plus 6 weeks corrected
arm group label: Unfortified Human Donor Milk
arm group type: Active Comparator
description: Used to make up any shortfall in mother's own milk
arm group label: Fortified Human Donor Milk
arm group type: Active Comparator
description: Used to make up any shortfall in mother's own milk
arm group label: Preterm Formula
arm group type: Active Comparator
description: Used to make up any shortfall in mother's own milk
intervention type: Other
intervention name: Unfortified Human donor Milk used to make up any shortfall in mother's own milk
arm group label: Unfortified Human Donor Milk
intervention type: Other
intervention name: Fortified Human donor Milk used to make up any shortfall in mother's own milk
arm group label: Fortified Human Donor Milk
intervention type: Other
intervention name: Preterm Formula used when there is a shortfall in mother's own milk
arm group label: Preterm Formula
criteria: 
gender: All
minimum age: 25 Weeks
maximum age: 31 Weeks
healthy volunteers: Accepts Healthy Volunteers
last name: Neena Modi, MBChB
role: Principal Investigator
affiliation: Imperial College London
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Insulin Resistance
submitted: September 30, 2021
returned: October 28, 2021
submitted: September 29, 2022
returned: August 18, 2023