Clinical trial NCT02554630: Novel Mechanisms and Approaches to Treat Neonatal Sepsis
Official title: Novel Mechanisms and Approaches to Treat Neonatal Sepsis: Adjuvant Therapies, Host Microbiome, and Genomic Expression and Functional Capacity of Innate Immune Cells
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Complication of Prematurity
Immunologic Deficiency Syndromes
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
name: Surgical Infection Society
First posted: 2015-09-18
Enrollment: 142
Sex: ALL
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Preterm neonates 0-72 hours old Term Neonates 0-72 hours old Healthy Adult Controls 18-55 years old

Brief summary: 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.

Detailed description: 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;

1. 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.
2. 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:

   1. 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.
   2. 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.
3. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Genomic analysis
timeFrame: Day 1
measure: Functional immunologic analysis
timeFrame: Day 1
Secondary outcomes:
measure: Immune Function Correlation with Clinical Outcomes
timeFrame: 90 days
measure: Ex-vivo Adjuvant Therapies On Immune Function
timeFrame: Day 1
measure: Ex-vivo Adjuvant Therapies Effect On Immune Cell Genomic Expression
timeFrame: Day 1
measure: Microbiome Influences Immune Cell Function
timeFrame: Day 1
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: UF Health
state: Florida
Study officials:
affiliation: University of Florida
name: Shawn Larson, MD
role: PRINCIPAL_INVESTIGATOR
References:
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