Transfusion-related Inflammatory Cytokine and Neutrophil Extracellular Trap Quantification in Neonates

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Utah
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT01735552
First received: November 22, 2012
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

Despite many advances in neonatal care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality among premature infants. NEC is the most common life-threatening gastrointestinal emergency encountered in the neonatal intensive care unit, affecting between 3.8% and 13% of very low birthweight (VLBW) infants (1-3). More recently interest has intensified regarding the possible association between "elective" red blood cell (RBC) transfusions in premature infants and the subsequent development of NEC (4-9). On a physiological basis, a few explanations for transfusion-associated NEC have been proposed: 1) the physiological impact of anemia that can initiate a cascade of events leading to ischemic-hypoxemic mucosal gut injury predisposing to NEC [10]; and 2) increased splanchnic blood flow following RBC transfusion leading to reperfusion injury of gut mucosa.

Aim 1. This study will quantify inflammatory cytokine profiles in anemic infants cared for in the NICU prior to and after transfusion with packed red blood cells (PRBC), as dictated by current clinical guidelines for treatment of anemia, and prospectively assess for clinical signs and symptoms of NEC following each transfusion event.

Aim 2. Polymorphonuclear leukocytes (PMNs) isolated from the pre- and post-transfusion blood samples will be assessed in vitro for neutrophil extracellular traps (NET) formation.

Aim 3. A) To determine whether significant anemia preceding a RBC transfusion is associated with impaired intestinal oxygenation, and whether a RBC transfusion temporarily increases splanchnic oxygenation. We postulate that the CSOR will be low (<0.75) at baseline measurement in infants with hemodynamically significant anemia, and that RBC transfusion will temporarily increase intestinal perfusion in that particular group of babies.

B) To determine whether alterations in mesenteric regional oxygenation saturation(rSO2) can predict the development of NEC in VLBW infants. We hypothesize that overall cerebro-splanchnic oxygenation ratio (CSOR) values will be significantly lower among very low birth weight (VLBW) infants that develop NEC, when compared to CSOR values obtained in infants that do not develop NEC following RBC transfusion.


Condition
Anemia of Prematurity
Necrotizing Enterocolitis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Transfusion-related Inflammatory Cytokine and Neutrophil Extracellular Trap Quantification in Neonates.

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Serum cytokine content [ Time Frame: 6 hrs ] [ Designated as safety issue: No ]
    Plasma samples will be analyzed for the protein content of 13 different cytokines via a multiplexed sandwich capture assay performed at the ARUP Institute for Experimental and Clinical Pathology. The cytokines and chemokines assayed will include: CD40 ligand, interferon-gamma, interleukin-10, interleukin-12, interleukin-13, interleukin-1-β, interleukin-2, interleukin-2-receptor, interleukin-4, interleukin-5, interleukin-6, IL-8, and Tumor Necrosis Factor-alpha. In addition, we will assay components of the complement pathway including: total hemolytic complement, C3a, C5a, and FAB fragments in the alternative complement pathway. Cytokine protein levels before and after transfusion will be compared to each other and to the PRBC sample cytokine content.


Secondary Outcome Measures:
  • Assessment of NET formation [ Time Frame: 6 hrs ] [ Designated as safety issue: No ]
    PMNs will be isolated from the participant blood samples following removal of the plasma via positive immunoselection. They will then be stimulated in vitro with NET-inducing stimuli such as lipopolysaccharide or platelet-activating factor for 1 hour under standard conditions and assayed for NET formation both qualitatively via confocal microscopy and quantitatively via histone H3 supernatant content as determined by ELISA and/or western blotting.


Other Outcome Measures:
  • Tissue oxygenation indexes (TOI) of cerebral (TOI brain ) and splanchnic (TOIabdo) regions [ Time Frame: 53 hrs ] [ Designated as safety issue: No ]
    Tissue oxygenation indexes (TOI) of cerebral (TOI brain ) and splanchnic (TOIabdo) regions will be measured using NIRS and the values reported as CSOR (TOIabdo/TOI brain). Measurements will be continuously recorded and data points obtained for 30 minute periods at baseline or T0 (prior to PRBC transfusion), and every hour during the RBC transfusion (T1, T2, T3 and T4)

  • Mesenteric rSO2 [ Time Frame: 53 hrs ] [ Designated as safety issue: No ]

    To determine whether alterations in mesenteric rSO2 can predict the development of NEC in VLBW infants.

    For this aim, TOI and CSOR will be measured every 3 hours for 30 minute periods in the first 48 hours following RBC transfusion (T5 to T16)(Table 1). By obtaining measurements during this time frame, we intend to capture the period of greatest susceptibility to develop NEC in this population.



Estimated Enrollment: 200
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Infants requiring PRBCs
Premature infants who require PRBCs for anemia that is not related to sepsis, surgery, NEC or immunologic abnormalities.

  Eligibility

Ages Eligible for Study:   up to 12 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Premature infants admitted into the University of Utah (UUMC), Primary Children's Medical Center (PCMC) and Intermountain Medical Center's (IMC) Neonatal Intesive Care Unit (NICUs)

Criteria

Inclusion Criteria:

  • Inpatient in NICU at UUMC, PCMC, or IMC
  • Gestational age at birth ≤ 32 weeks
  • Birth weight ≤ 1500 grams
  • Age ≤ 12 weeks of life

Exclusion Criteria:

  • Lack of parental consent
  • Multiple congenital anomalies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735552

Contacts
Contact: Carrie Rau, RN 801-213-3360 carrie.rau@hsc.utah.edu

Locations
United States, Utah
Intermountain Medical Center Recruiting
Murray, Utah, United States, 84107
Contact: Carrie Rau, RN    801-213-3360    carrie.rau@hsc.utah.edu   
Contact: , M.D.         
Sub-Investigator: Mariana Baserga, M.D.         
Principal Investigator: Susan Wiedmeier, MD         
Primary Children's Medical Center Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Carrie Rau, RN    801-213-3360    carrie.rau@hsc.utah.edu   
Principal Investigator: Susan Wiedmeier, MD         
Sub-Investigator: Mariana Baserga, MD         
University of Utah Hospital Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Carrie Rau, RN    801-213-3360    carrie.rau@hsc.utah.edu   
Principal Investigator: Susan Wiedmeier, MD         
Sub-Investigator: Mariana Baserga, MD         
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Susan Wiedmeier, MD University of Utah
Principal Investigator: Mariana Baserga, MD University of Utah
  More Information

Publications:
Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT01735552     History of Changes
Other Study ID Numbers: 51050
Study First Received: November 22, 2012
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
gut reperfusion injury
blood transfusions
premature infants
anemia
regional oxygen saturations
necrotizing enterocolitis
mesenteric oxygenation

Additional relevant MeSH terms:
Anemia, Neonatal
Enterocolitis
Enterocolitis, Necrotizing
Infant, Premature, Diseases
Anemia
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Hematologic Diseases
Infant, Newborn, Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on October 20, 2014