Microfluidic Assessment of Clinical Outcomes in Preterm Newborns

Neonatal SEPSIS Clinical Trial

Official title:

Microfluidic Assessment of Clinical Outcomes in Preterm Newborns

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03291496
• Other study ID #: IRB201701566 N
• Secondary ID: R01HD089939OCR26
• Status: Active, not recruiting
• Start date: November 14, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 293
• Est. completion date: December 31, 2024
• Est. primary completion date: May 10, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 23 Weeks to 42 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Neonatal SEPSIS

Intervention

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.
• Blood Collection Term
A single 250 µl blood sample will be collected once the term neonate is >24 hours old.
• Adult Blood collection
One Time 1 ml of whole blood collected

Locations

Country	Name	City	State
United States	UF Health	Gainesville	Florida

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (33)

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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. — View 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. — View Citation

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prediction of Sepsis in Premature Neonates	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.	Days 4-21
Secondary	Neutrophil Function of Premature Neonate during Development	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	Days 22-180