Microfluidic Assessment of Clinical Outcomes in Preterm Newborns

Sponsor

University of Florida (Other)

Overall Status

Recruiting

CT.gov ID

NCT03291496

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

840

Enrollment

Location

54.5

Anticipated Duration (Months)

15.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neonatal SEPSIS	Other: Blood Collection Preterm Other: Blood Collection Term Other: Adult Blood collection

Detailed Description

Blood samples will be collected from two populations: preterm infants and term infants.

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.
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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

840 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Microfluidic Assessment of Clinical Outcomes in Preterm Newborns

Actual Study Start Date :

Nov 14, 2017

Anticipated Primary Completion Date :

May 31, 2022

Anticipated Study Completion Date :

May 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Preterm Neonates Blood collection Preterm. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.	Other: Blood Collection Preterm 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.
Term Neonates Blood collection Term. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.	Other: Blood Collection Term A single 250 µl blood sample will be collected once the term neonate is >24 hours old.
Healthy Adult One-time whole blood draw of 1ml collection	Other: Adult Blood collection One Time 1 ml of whole blood collected

Arm

Intervention/Treatment

Preterm Neonates

Blood collection Preterm. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.

Other: Blood Collection Preterm

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.

Term Neonates

Blood collection Term. From blood, the speed, directionality, and persistence of PMN chemotaxis using microfluidic devices and transcriptomic analysis will be measured.

Other: Blood Collection Term

A single 250 µl blood sample will be collected once the term neonate is >24 hours old.

Healthy Adult

One-time whole blood draw of 1ml collection

Other: Adult Blood collection

One Time 1 ml of whole blood collected

Outcome Measures

Primary Outcome Measures

Prediction of Sepsis in Premature Neonates [Days 4-21]
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.

Secondary Outcome Measures

Neutrophil Function of Premature Neonate during Development [Days 22-180]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

23 Weeks to 42 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

For preterm neonates <32 weeks gestation at birth with no known or suspected congenital anomalies.
For term neonates >36 weeks gestation at birth with no known or suspected congenital anomalies.

Exclusion Criteria:

Congenital defects, suspected genetic disorders, 32-36 weeks completed gestation, or lack of consent.

Healthy Adult:

Inclusion criteria Between the ages of 18 and 65 years of age
Exclusion Criteria Taking any immune modifying medications or have an active immune modifying disease process

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UF Health	Gainesville	Florida	United States	32610

Sponsors and Collaborators

University of Florida
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator: James L Wynn, MD, University of Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of Florida

ClinicalTrials.gov Identifier:

NCT03291496

Other Study ID Numbers:

IRB201701566 N
R01HD089939
OCR26202

First Posted:

Sep 25, 2017

Last Update Posted:

Jun 24, 2021

Last Verified:

Jun 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neonatal Sepsis

Study Results

No Results Posted as of Jun 24, 2021