<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/NCT03291496</url>
  </required_header>
  <id_info>
    <org_study_id>IRB201701566 N</org_study_id>
    <secondary_id>R01HD089939</secondary_id>
    <secondary_id>OCR26202</secondary_id>
    <nct_id>NCT03291496</nct_id>
  </id_info>
  <brief_title>Microfluidic Assessment of Clinical Outcomes in Preterm Newborns</brief_title>
  <official_title>Microfluidic Assessment of Clinical Outcomes in Preterm Newborns</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>No</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>
      Sepsis has its greatest impact in the prematurely born (preterm) population. Neonatal sepsis&#xD;
      (sepsis within the first month of life) causes over one million deaths worldwide annually,&#xD;
      and is one of the most common, difficult and costly problems to diagnose, treat and prevent.&#xD;
      The preterm infant can suffer rates of sepsis up to 1000-fold higher than the full-term&#xD;
      infant, and bears the brunt of the associated mortality and lifelong sepsis-survivor&#xD;
      morbidity.&#xD;
&#xD;
      The project is enabled by several novel, validated, microfluidic technologies that are robust&#xD;
      and easy to use with little training. These technologies provide comprehensive measures of&#xD;
      the functionality of blood PMN population; a critical cellular component of innate immunity.&#xD;
      The study team will also extract high-quality nucleic acids from microfluidic-sorted PMNs for&#xD;
      transcriptomic analyses. Collectively, these techniques require a total of 250 microliters&#xD;
      (µL) of blood, which makes them particularly useful for preterm infants where sample volume&#xD;
      is limited, and facilitates serial assessments with unprecedented temporal resolution of key&#xD;
      functions of PMNs.&#xD;
&#xD;
      These studies, integrated with bioinformatics approaches, will generate new tools for&#xD;
      diagnosing sepsis in the newborn and predicting clinical outcomes. Such approaches have the&#xD;
      capability to dramatically change the clinical management of the preterm infant, and&#xD;
      potentially improve long-term outcomes while reducing hospital costs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Blood samples will be collected from two populations: preterm infants and term infants.&#xD;
&#xD;
        1. Preterm neonates (&lt;32 weeks) the study team will collect a baseline 250 µl blood sample&#xD;
           on day four of life and then approximately every three days, as is possible, until&#xD;
           twenty-one days of life. In addition, for preterm neonates who have suspected sepsis, an&#xD;
           additional 250 µl blood sample will be obtained on the day of suspected sepsis. After&#xD;
           day twenty-one of life, 250 µl blood will be sampled one time per week until discharge,&#xD;
           when a final 250 µl blood sample will be collected. The amount drawn for study related&#xD;
           blood collections will not exceed the lesser of 50 ml or 3.0 ml/kg in an 8-week period.&#xD;
&#xD;
        2. Term neonates (&gt;36 weeks) the study team will be collect a single 250 µl blood sample&#xD;
           with the routine screen for metabolic disorders when they are &gt;24 hours old. This will&#xD;
           be the only study related blood collection for term neonates.&#xD;
&#xD;
      For all infants, term and preterm, the following data will be collected while the neonate is&#xD;
      hospitalized: Demographic information (age, date of birth), past and present medical records,&#xD;
      laboratory, microbiology, and all other test results, X-ray, CT, MRI, US and all other&#xD;
      imaging test results, records about any medication received during admission, records of&#xD;
      physical exam during admission, records of all vital signs and hemodynamic monitoring during&#xD;
      admission, records of any procedure or intervention during admission, and condition at the&#xD;
      discharge and discharge location.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 14, 2017</start_date>
  <completion_date type="Anticipated">May 31, 2023</completion_date>
  <primary_completion_date type="Actual">May 10, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Prediction of Sepsis in Premature Neonates</measure>
    <time_frame>Days 4-21</time_frame>
    <description>The study team will determine whether blood neutrophil migration phenotype using a microfluidic-based approach can be used to predict the onset of sepsis, as well as poor outcome from sepsis, in premature neonates. From peripheral blood, the study team will measure speed, directionality, and persistence of neutrophil chemotaxis using microfluidic devices. The goal is to prospectively identify and validate biomarkers that can stratify neonates who will become septic and have a protracted clinical course. To complement these functional assays, the study team will determine if transcriptomic profiling adds to the diagnostic resolution generated through these functional analyses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neutrophil Function of Premature Neonate during Development</measure>
    <time_frame>Days 22-180</time_frame>
    <description>The study team will determine whether premature neonates restore a more normal neutrophil migration phenotype and genomic profile as they reach their developmental milestones during NICU admission</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">293</enrollment>
  <condition>Neonatal SEPSIS</condition>
  <arm_group>
    <arm_group_label>Preterm Neonates</arm_group_label>
    <description>Blood collection Preterm. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Term Neonates</arm_group_label>
    <description>Blood collection Term. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Adult</arm_group_label>
    <description>One-time whole blood draw of 1ml collection</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood Collection Preterm</intervention_name>
    <description>Blood will be collected on day 4 of life and then approximately every 3 days until 21 days of life. Thereafter, one sample will be collected weekly until discharge. For preterm neonates that have suspected sepsis an additional sample will be collected within 24-48 hours of the initial sepsis evaluation.</description>
    <arm_group_label>Preterm Neonates</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood Collection Term</intervention_name>
    <description>A single 250 µl blood sample will be collected once the term neonate is &gt;24 hours old.</description>
    <arm_group_label>Term Neonates</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Adult Blood collection</intervention_name>
    <description>One Time 1 ml of whole blood collected</description>
    <arm_group_label>Healthy Adult</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Preterm neonates &lt;32 weeks gestation. Term neonates &gt;36 weeks gestation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For preterm neonates &lt;32 weeks gestation at birth with no known or suspected&#xD;
             congenital anomalies.&#xD;
&#xD;
          -  For term neonates &gt;36 weeks gestation at birth with no known or suspected congenital&#xD;
             anomalies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Congenital defects, suspected genetic disorders, 32-36 weeks completed gestation, or&#xD;
             lack of consent.&#xD;
&#xD;
        Healthy Adult:&#xD;
&#xD;
          -  Inclusion criteria Between the ages of 18 and 65 years of age&#xD;
&#xD;
          -  Exclusion Criteria Taking any immune modifying medications or have an active immune&#xD;
             modifying disease process&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>23 Weeks</minimum_age>
    <maximum_age>42 Weeks</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James L Wynn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UF Health</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M, Mathers C, Black RE; Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012 Jun 9;379(9832):2151-61. doi: 10.1016/S0140-6736(12)60560-1. Epub 2012 May 11. Erratum In: Lancet. 2012 Oct 13;380(9850):1308.</citation>
    <PMID>22579125</PMID>
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    <PMID>12140299</PMID>
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    <PMID>22682464</PMID>
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    <citation>Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics. 2006 Jun;117(6):1979-87. doi: 10.1542/peds.2005-1707.</citation>
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    <citation>Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG. Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics. 2008 Apr;121(4):689-96. doi: 10.1542/peds.2007-2171.</citation>
    <PMID>18381532</PMID>
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    <citation>Hill DA, Hoffmann C, Abt MC, Du Y, Kobuley D, Kirn TJ, Bushman FD, Artis D. Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 2010 Mar;3(2):148-58. doi: 10.1038/mi.2009.132. Epub 2009 Nov 25.</citation>
    <PMID>19940845</PMID>
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    <citation>Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology (Reading). 2010 Nov;156(Pt 11):3216-3223. doi: 10.1099/mic.0.040618-0. Epub 2010 Aug 12.</citation>
    <PMID>20705661</PMID>
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    <citation>Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sanchez PJ, Ambalavanan N, Benjamin DK Jr; NICHD Neonatal Research Network. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics. 2009 Jan;123(1):58-66. doi: 10.1542/peds.2007-3423.</citation>
    <PMID>19117861</PMID>
  </reference>
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    <citation>Sjogren YM, Tomicic S, Lundberg A, Bottcher MF, Bjorksten B, Sverremark-Ekstrom E, Jenmalm MC. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clin Exp Allergy. 2009 Dec;39(12):1842-51. doi: 10.1111/j.1365-2222.2009.03326.x. Epub 2009 Sep 3.</citation>
    <PMID>19735274</PMID>
  </reference>
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    <citation>Wynn JL, Neu J, Moldawer LL, Levy O. Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis. J Perinatol. 2009 Feb;29(2):79-88. doi: 10.1038/jp.2008.132. Epub 2008 Sep 4. Erratum In: J Perinatol. 2009 Jul;29(7):527.</citation>
    <PMID>18769381</PMID>
  </reference>
  <reference>
    <citation>Wynn J, Cornell TT, Wong HR, Shanley TP, Wheeler DS. The host response to sepsis and developmental impact. Pediatrics. 2010 May;125(5):1031-41. doi: 10.1542/peds.2009-3301. Epub 2010 Apr 26.</citation>
    <PMID>20421258</PMID>
  </reference>
  <reference>
    <citation>Strunk T, Currie A, Richmond P, Simmer K, Burgner D. Innate immunity in human newborn infants: prematurity means more than immaturity. J Matern Fetal Neonatal Med. 2011 Jan;24(1):25-31. doi: 10.3109/14767058.2010.482605. Epub 2010 Jun 23.</citation>
    <PMID>20569168</PMID>
  </reference>
  <reference>
    <citation>Wynn JL, Scumpia PO, Winfield RD, Delano MJ, Kelly-Scumpia K, Barker T, Ungaro R, Levy O, Moldawer LL. Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists. Blood. 2008 Sep 1;112(5):1750-8. doi: 10.1182/blood-2008-01-130500. Epub 2008 Jun 30.</citation>
    <PMID>18591384</PMID>
  </reference>
  <reference>
    <citation>Wynn JL, Scumpia PO, Delano MJ, O'Malley KA, Ungaro R, Abouhamze A, Moldawer LL. Increased mortality and altered immunity in neonatal sepsis produced by generalized peritonitis. Shock. 2007 Dec;28(6):675-683. doi: 10.1097/SHK.0b013e3180556d09.</citation>
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    <citation>PrabhuDas M, Adkins B, Gans H, King C, Levy O, Ramilo O, Siegrist CA. Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol. 2011 Mar;12(3):189-94. doi: 10.1038/ni0311-189. No abstract available.</citation>
    <PMID>21321588</PMID>
  </reference>
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    <citation>Wynn JL, Cvijanovich NZ, Allen GL, Thomas NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Lin R, Shanley TP, Bigham MT, Banschbach S, Beckman E, Wong HR. The influence of developmental age on the early transcriptomic response of children with septic shock. Mol Med. 2011;17(11-12):1146-56. doi: 10.2119/molmed.2011.00169. Epub 2011 Jul 5.</citation>
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  </reference>
  <reference>
    <citation>Wynn JL, Guthrie SO, Wong HR, Lahni P, Ungaro R, Lopez MC, Baker HV, Moldawer LL. Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis. Mol Med. 2015 Jun 2;21(1):496-504. doi: 10.2119/molmed.2015.00064.</citation>
    <PMID>26052715</PMID>
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    <PMID>16498448</PMID>
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    <PMID>450562</PMID>
  </reference>
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    <citation>Wong HR, Freishtat RJ, Monaco M, Odoms K, Shanley TP. Leukocyte subset-derived genomewide expression profiles in pediatric septic shock. Pediatr Crit Care Med. 2010 May;11(3):349-55. doi: 10.1097/PCC.0b013e3181c519b4.</citation>
    <PMID>20009785</PMID>
  </reference>
  <reference>
    <citation>Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates. Clin Perinatol. 2010 Jun;37(2):439-79. doi: 10.1016/j.clp.2010.04.002.</citation>
    <PMID>20569817</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>September 14, 2022</last_update_submitted>
  <last_update_submitted_qc>September 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2022</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>Neonatal Sepsis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03291496
org study id: IRB201701566 N
secondary id: R01HD089939
secondary id: OCR26202
nct id: NCT03291496
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Sepsis has its greatest impact in the prematurely born (preterm) population. Neonatal sepsis
      (sepsis within the first month of life) causes over one million deaths worldwide annually,
      and is one of the most common, difficult and costly problems to diagnose, treat and prevent.
      The preterm infant can suffer rates of sepsis up to 1000-fold higher than the full-term
      infant, and bears the brunt of the associated mortality and lifelong sepsis-survivor
      morbidity.

      The project is enabled by several novel, validated, microfluidic technologies that are robust
      and easy to use with little training. These technologies provide comprehensive measures of
      the functionality of blood PMN population; a critical cellular component of innate immunity.
      The study team will also extract high-quality nucleic acids from microfluidic-sorted PMNs for
      transcriptomic analyses. Collectively, these techniques require a total of 250 microliters
      (µL) of blood, which makes them particularly useful for preterm infants where sample volume
      is limited, and facilitates serial assessments with unprecedented temporal resolution of key
      functions of PMNs.

      These studies, integrated with bioinformatics approaches, will generate new tools for
      diagnosing sepsis in the newborn and predicting clinical outcomes. Such approaches have the
      capability to dramatically change the clinical management of the preterm infant, and
      potentially improve long-term outcomes while reducing hospital costs.
Blood samples will be collected from two populations: preterm infants and term infants.

        1. Preterm neonates (<32 weeks) the study team will collect a baseline 250 µl blood sample
           on day four of life and then approximately every three days, as is possible, until
           twenty-one days of life. In addition, for preterm neonates who have suspected sepsis, an
           additional 250 µl blood sample will be obtained on the day of suspected sepsis. After
           day twenty-one of life, 250 µl blood will be sampled one time per week until discharge,
           when a final 250 µl blood sample will be collected. The amount drawn for study related
           blood collections will not exceed the lesser of 50 ml or 3.0 ml/kg in an 8-week period.

        2. Term neonates (>36 weeks) the study team will be collect a single 250 µl blood sample
           with the routine screen for metabolic disorders when they are >24 hours old. This will
           be the only study related blood collection for term neonates.

      For all infants, term and preterm, the following data will be collected while the neonate is
      hospitalized: Demographic information (age, date of birth), past and present medical records,
      laboratory, microbiology, and all other test results, X-ray, CT, MRI, US and all other
      imaging test results, records about any medication received during admission, records of
      physical exam during admission, records of all vital signs and hemodynamic monitoring during
      admission, records of any procedure or intervention during admission, and condition at the
      discharge and discharge location.
observational model: Cohort
time perspective: Prospective
measure: Prediction of Sepsis in Premature Neonates
time frame: Days 4-21
description: The study team will determine whether blood neutrophil migration phenotype using a microfluidic-based approach can be used to predict the onset of sepsis, as well as poor outcome from sepsis, in premature neonates. From peripheral blood, the study team will measure speed, directionality, and persistence of neutrophil chemotaxis using microfluidic devices. The goal is to prospectively identify and validate biomarkers that can stratify neonates who will become septic and have a protracted clinical course. To complement these functional assays, the study team will determine if transcriptomic profiling adds to the diagnostic resolution generated through these functional analyses.
measure: Neutrophil Function of Premature Neonate during Development
time frame: Days 22-180
description: The study team will determine whether premature neonates restore a more normal neutrophil migration phenotype and genomic profile as they reach their developmental milestones during NICU admission
arm group label: Preterm Neonates
description: Blood collection Preterm. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.
arm group label: Term Neonates
description: Blood collection Term. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.
arm group label: Healthy Adult
description: One-time whole blood draw of 1ml collection
intervention type: Other
intervention name: Blood Collection Preterm
description: Blood will be collected on day 4 of life and then approximately every 3 days until 21 days of life. Thereafter, one sample will be collected weekly until discharge. For preterm neonates that have suspected sepsis an additional sample will be collected within 24-48 hours of the initial sepsis evaluation.
arm group label: Preterm Neonates
intervention type: Other
intervention name: Blood Collection Term
description: A single 250 µl blood sample will be collected once the term neonate is >24 hours old.
arm group label: Term Neonates
intervention type: Other
intervention name: Adult Blood collection
description: One Time 1 ml of whole blood collected
arm group label: Healthy Adult
Blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 23 Weeks
maximum age: 42 Weeks
healthy volunteers: Accepts Healthy Volunteers
last name: James L Wynn, MD
role: Principal Investigator
affiliation: University of Florida
facility: 
country: United States
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PMID: 20569817
responsible party type: Sponsor
mesh term: Neonatal Sepsis
sharing ipd: Undecided