Skip to main content
OpenTrials
Completed

NCT Number: NCT02554630

Novel Mechanisms and Approaches to Treat Neonatal Sepsis

Mortality related to neonatal sepsis exceeds 1 million deaths worldwide; the highest risk of mortality is in preterm neonates, especially low birth weight (LBW), and very low birth weight (VLBW) neonates. The estimated cost of caring for these patients is approximately $700 million in the US alone.

In an effort to help mature the neonatal immune system, several adjuvant therapies have been studied; however, none have been implemented in clinical practice. One of the most frequently considered targets for adjuvant therapy is toll-like receptors (TLRs). TLRs detect conserved molecular products of microorganisms (lipopolysaccharide (LPS), and initiate immunity and inflammation. Early adjuvant administration in VLBW infants may be a viable approach to reducing the incidence of early and late sepsis.

This research study will characterize immune genomic expression and functional capacity at the time of birth in both term and preterm neonates and determine what effects, if any, that adjuvants have on this function. Additionally, this study will seek to determine if immune function correlates with certain microbiota.

Completed

Looking for future studies?

Notify Me

Key information

Age range

Up to 55 year

Sex eligibility

All sexes

Study type

Observational

Primary location

UF Health

Gainesville, Florida, 32610, United States

About this study

Blood samples will be collected from three populations: preterm infants, term infants and healthy adult controls. In addition, a collection of meconium (<1mL) from the diaper of these term and preterm neonates;

  • Term neonates (gestational age 37-42 weeks) between birth and 72 hours of life who have blood collected for the following clinical indications:

a. Blood will be collected at 0-72 hours of life from neonates that are undergoing state metabolic screens or for clinical evaluation jaundice. The sample will be obtained during the standard of care state metabolic screen or for clinical evaluation of jaundice. The neonate will only have an extra drop of blood placed (500-700 micro-liters) in a tube during the heel sticks. Neonates will only have 1 sample drawn throughout the duration of the study.

  • Preterm neonates (gestational age 24-37 weeks) consisting of two populations between birth and 72 hours of life who have blood collected for the following clinical indications:
  • Blood will be collected at 0-72 hours of life from neonates that are otherwise healthy and do not require additional laboratory testing who are undergoing state metabolic screens or for evaluation of jaundice. The neonate will only have an extra drop of blood placed (500-700 microliters) in a tube during the heel stick. Neonates will only have 1 sample drawn throughout the duration of the study.
  • A second group of premature neonates will have blood drawn for complications related to prematurity (sepsis work-up). The neonate will only have an extra drop of blood placed (500-700 micro-liters) in a tube during one of these clinical blood draws.
  • Healthy adult controls will have (4milleters) blood collected by way of vein puncture.

For all infants, term and preterm, the following data will be collected at the time of blood collection: gender, gestational age, weight, mechanism of birth (vaginal vs cesarean section), evidence of infectious complication (chorioamnionitis, prolonged rupture of membranes, maternal group B strep colonization, hypoglycemia), use of perinatal antibiotics or steroids, laboratory values available in the electronic medial record (CBC, CMP, Lactic acid, CRP) and Apgar scores will be collected from each patient. Additionally the clinical outcomes of these patients, term and preterm,will be collected until time of discharge but not to exceed 90 days.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Preterm and Term neonates 0-72 hours old

Inclusion criteria

  • Consent to participate in the study

Exclusion criteria

  • non- survivable condition

Healthy Adult Controls

Inclusion criteria

  • Consent to participate in the study
  • Age >18 years old, <55 years old

Exclusion criteria

  • Age <18 years old, >55 years old
  • Severe pre-existing organ dysfunction
  • Oncolytic therapy within 14 days
  • HIV positive status
  • Current use of chronic steroids

Treatment and study plan

Adjuvant

Other

Blood will be incubated, ex-vivo, with one of the adjuvant therapies or no adjuvant and then, using microfluidic techniques the immune genomic profile and the functional capacity of immune cells will be assessed.

Other names: Lippopolysaccaride, Specific toll-like receptor 4 agonist, Non-specific toll-like receptor 4 agonist

Blood collection

Other

Blood collection will be performed on all groups.

Primary outcomes

  1. Genomic analysis

    Time frame: Day 1

    The genomic profile will be interpreted using Ingenuity Pathway Analysis (IPA) software to make functional predictions. Additionally, a cytokine analysis, and an evaluation for the prevalence of myeloid derived suppressor cells (MDSCs) that have been shown to correlate with poorer outcomes in adult sepsis studies will be performed.

  2. Functional immunologic analysis

    Time frame: Day 1

    Functional capacity will be confirmed directly by observing chemotaxis and quantifying generation of reactive oxygen species (ROS), rate of phagocytosis, and bacterial killing ability. Additionally, a cytokine analysis, and an evaluation for the prevalence of myeloid derived suppressor cells (MDSCs) that have been shown to correlate with poorer outcomes in adult sepsis studies will be performed.

Secondary outcomes

  1. Immune Function Correlation with Clinical Outcomes

    Time frame: 90 days

    The clinical course of these neonates will be followed for incidence of infectious complications including sepsis as evident by culture results. Therefore, allowing the investigators to determine if immunologic deficits present at birth correlate with clinical outcomes.

  2. Ex-vivo Adjuvant Therapies On Immune Function

    Time frame: Day 1

    The implementation of adjuvants in both murine and human models has shown improved function of immune effector cells as well as in clinical outcomes. Adjuvant treatment of mice with TLR agonists stimulates polymorphonuclear leukocytes (PMN) recruitment and function, decreases rates of bacteremia, and increases survival to polymicrobial and gram negative sepsis. Vaccination with Bacillus Calmette-Guerin (BCG) at birth reduces mortality by 40% in LBW infants to sepsis (not tuberculosis) in sub-Saharan Africa. Utilizing an ex-vivo design we will evaluate the changes in immune cell functional capacity.

  3. Ex-vivo Adjuvant Therapies Effect On Immune Cell Genomic Expression

    Time frame: Day 1

    The implementation of adjuvants in both murine and human models has shown improved function of immune effector cells as well as in clinical outcomes. Adjuvant treatment of mice with TLR agonists stimulates polymorphonuclear leukocytes (PMN) recruitment and function, decreases rates of bacteremia, and increases survival to polymicrobial and gram negative sepsis. Vaccination with Bacillus Calmette-Guerin (BCG) at birth reduces mortality by 40% in LBW infants to sepsis (not tuberculosis) in sub-Saharan Africa. Utilizing an ex-vivo design we will evaluate the changes in immune cell genomic expression.

  4. Microbiome Influences Immune Cell Function

    Time frame: Day 1

    Correlated immune deficiencies with differences in the microbiome at the time of birth will be documented by using microbiomic differences present at the time of birth in term vs preterm neonates using Illumina 16s rRNA technology. This system uses highly conserved sequences among bacteria to identify and classify bacterium. The software then provides taxonomic classification to find a microbiomic signature that is specific to immune dysfunction.

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Collaborators

  • National Institute of General Medical Sciences (NIGMS)
  • Surgical Infection Society

Registry information

Official study title

Novel Mechanisms and Approaches to Treat Neonatal Sepsis: Adjuvant Therapies, Host Microbiome, and Genomic Expression and Functional Capacity of Innate Immune Cells

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Sep 18, 2015
Registry last updated
Feb 10, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.