Clinical trial NCT00371241: Antibody Secreting Cell and Cyotokine Profiles in Neonates on ECMO
Official title: Antibody Secreting Cell (ASC) and Immunoactive Protein Profiles in Neonates on Extracorporeal Membrane Oxygenation (ECMO)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Persistent Fetal Circulation Syndrome
Diaphragmatic Hernia
Meconium Aspiration
Sepsis
Keywords: ECMO
extracorporeal membrane oxygenation
cytokines
chemokines
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Memorial Hermann Hospital
First posted: 2006-09-04
Enrollment: 12
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Infants requiring ECMO

Brief summary: Infants are placed on ECMO for correction of reversible respiratory failure. Often, because a few of the reasons for respiratory failure show us similar things in the baby, it is difficult to determine exactly which is causing the biggest problem. We are now capable of measuring certain cells and proteins in these infants that may help us more accurately diagnose the exact problem. We hypothesize that infants placed on ECMO will show unique antibody-secreting cells responses and patterns of cytokine and chemokine (protein) response to illness and to the ECMO circuit. If we find unique patterns to these cells or proteins, they may be able to predict outcomes or guide treatment of these infants.

Detailed description: Specific Aims Primary Objective

1. Determine the rise, peak, and fall of immunoglobulin isotype-specific ASC's, and immunoactive proteins (cytokines and chemokines) from sequential samples of peripheral blood from infants on ECMO.

Secondary Objectives:

1. Determine the most appropriate time to sample blood from infants with suspected sepsis for ASC diagnostic assay.
2. Characterize the incidence of culture-negative sepsis that leads to ECMO.
3. Determine immunoglobulin isotype-specific levels of ASC in infants with and without infection.
4. Establish an archive of mononuclear cells and plasma to use in development of pathogen specific ASC assays.

Hypothesis Infants on ECMO will have a high ASC response and unique cytokine/chemokine patterns due to possible underlying infection and exposure to many foreign antigens (blood products, ECMO circuit). A significant portion of these will have ASC's with specificity for common causes of neonatal sepsis that is not detected by routine blood culture.

Procedures:

Residual samples will be collected from those used in routine procedures for infants on ECMO. The approximate volume/sample will be 0.5-0.8ml. Specimens will be processed using methods well established in our laboratory. Briefly, PBMC's will be isolated via Ficoll gradient and archived in liquid nitrogen at -80C. Batch analysis of ASC levels and lymphocyte proliferation activity will be performed when sufficient number of specimens are accumulated. A detailed profile and quantification of immune cells will be determined by Fluorescent Activated Cell Sorter (FACS) staining for CD3, CD4, CD8, CD27, CD38, CD45, and HLA-DR. A bead micro-array will be used to detect levels of immunoactive molecules, also done on the FACS. The proteins detected will include, but may not be limited to, the following: IL1β, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, IL17, GCSF, GMCSF, IFN-γ, MCP-1, MIP-1β, TNFα. The ASC procedure be that established by Van de Verg modified to use membrane surface microculture plates in place of agar with outcomes read by CTL analyzer in place of manual count. LPA assays will use long established techniques.

Eligibility criteria: Inclusion Criteria:

* 1) term newborn infants \>24 hours and ≤ 30 days old 2) Placed on ECMO in the NICU at MHCH 3) Parental consent obtained within 48 hours of being placed on ECMO

Exclusion Criteria:

* 1) Infant \> 30 days old 2) Infant NOT on ECMO 3) Withdrawal of parental consent

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
Study officials:
affiliation: University of Texas Health Science Center at Houston- Division of Infectious Diseases
name: James M Murpy, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Stoll BJ, Lee FK, Larsen S, Hale E, Schwartz D, Rice RJ, Ashby R, Holmes R, Nahmias AJ. Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma. J Infect Dis. 1993 May;167(5):1093-9. doi: 10.1093/infdis/167.5.1093.
citation: Baqar S, Nour El Din AA, Scott DA, Bourgeois AL, Mourad AS, Kleinosky MT, Oplinger MJ, Murphy JR. Standardization of measurement of immunoglobulin-secreting cells in human peripheral circulation. Clin Diagn Lab Immunol. 1997 May;4(3):375-9. doi: 10.1128/cdli.4.3.375-379.1997.
citation: Kuster H, Weiss M, Willeitner AE, Detlefsen S, Jeremias I, Zbojan J, Geiger R, Lipowsky G, Simbruner G. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet. 1998 Oct 17;352(9136):1271-7. doi: 10.1016/S0140-6736(98)08148-3.