Novel Mechanisms and Approaches to Treat Neonatal Sepsis

University of Florida

Status: Completed

Conditions: Complication of Prematurity; Immunologic Deficiency Syndromes

Treatments: Other: Adjuvant; Other: Blood Collection

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT02554630

R01GM097531 (U.S. NIH Grant/Contract)

IRB201500447 -N

Details and patient eligibility

About

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.

Full 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.

Enrollment: 142 patients

Sex: All

Ages: Under 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

142 participants in 3 patient groups

Preterm Neonate

Description:

Neonates of gestational age 24-37 weeks. Blood collection will be performed at the time of a clinically required heelstick or blood draw. Microfluidic techniques, utilizing whole blood, will be employed to characterize the baseline genomic profile and functional capacity of immune cells. Adjuvant drugs will be employed ex-vivo to determine if adjuvant therapies change genomic expression and bolster immune function. Meconium will be collected for microbiome analysis. Clinical outcomes will be recorded from the electronic medical record.

Treatment:

Other: Blood Collection

Other: Adjuvant

Term Neonates

Description:

Neonates of gestational age 37-42 weeks. Blood collection will be performed at the time of a clinically required heelstick or blood draw. Microfluidic techniques, utilizing whole blood, will be employed to characterize the baseline genomic profile and functional capacity of immune cells. Adjuvant drugs will be employed ex-vivo to determine if adjuvant therapies change genomic expression and bolster immune function. Meconium will be collected for microbiome analysis. Clinical outcomes will be recorded from the electronic medical record.

Treatment:

Other: Blood Collection

Other: Adjuvant

Healthy Adult Control

Description:

Healthy Adult aged 18-55 years will undergo a single blood collection by the way of vein puncture. Microfluidic techniques, utilizing whole blood, will be employed to evaluate the genomic profile and functional capacity of immune cells. Adjuvant drugs will be employed ex-vivo to determine if adjuvant therapies change genomic expression and bolster immune function.

Treatment:

Other: Blood Collection

Other: Adjuvant