Antibody Secreting Cell and Cyotokine Profiles in Neonates on ECMO - Full Text View

Sponsors and Collaborators:	The University of Texas Health Science Center, Houston Memorial Hermann Hospital
Information provided by:	The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:	NCT00371241

Purpose

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.

Condition
Persistent Fetal Circulation Syndrome Diaphragmatic Hernia Meconium Aspiration Sepsis

Study Type:	Observational
Study Design:	Cohort, Prospective
Official Title:	Antibody Secreting Cell (ASC) and Immunoactive Protein Profiles in Neonates on Extracorporeal Membrane Oxygenation (ECMO)

Resource links provided by NLM:

MedlinePlus related topics: Hernia Sepsis

U.S. FDA Resources

Further study details as provided by The University of Texas Health Science Center, Houston:

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Plasma and whole blood

Enrollment:	12
Study Start Date:	September 2006
Study Completion Date:	November 2007

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:

Determine the most appropriate time to sample blood from infants with suspected sepsis for ASC diagnostic assay.
Characterize the incidence of culture-negative sepsis that leads to ECMO.
Determine immunoglobulin isotype-specific levels of ASC in infants with and without infection.
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

Ages Eligible for Study:	up to 30 Days
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Infants requiring ECMO

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00371241

Locations

United States, Texas
Memorial Hermann Hospital
Houston, Texas, United States, 77030

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Memorial Hermann Hospital

Investigators

Principal Investigator:

James M Murpy, PhD

University of Texas Health Science Center at Houston- Division of Infectious Diseases

More Information

Publications:

Stoll BJ, Lee FK, Hale E, Schwartz D, Holmes R, Ashby R, Czerkinsky C, Nahmias AJ. Immunoglobulin secretion by the normal and the infected newborn infant. J Pediatr. 1993 May;122(5 Pt 1):780-6.

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.

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.

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.

Responsible Party:	The University of Texas Health Science Center, HoustonU ( James R. Murphy )
Study ID Numbers:	HSC-MS-06-0122
Study First Received:	August 30, 2006
Last Updated:	December 3, 2007
ClinicalTrials.gov Identifier:	NCT00371241 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center, Houston:

ECMO
extracorporeal membrane oxygenation
cytokines
chemokines

Study placed in the following topic categories:

Pathological Conditions, Anatomical
Meconium Aspiration Syndrome
Pregnancy Complications
Respiration Disorders
Antibodies
Sepsis
Fetal Diseases
Respiratory Tract Diseases

Hypertension, Pulmonary
Hernia
Lung Diseases
Persistent Fetal Circulation Syndrome
Hernia, Diaphragmatic
Infant, Newborn, Diseases
Immunoglobulins
Hypertension

Additional relevant MeSH terms:

Pathological Conditions, Anatomical
Meconium Aspiration Syndrome
Disease
Pregnancy Complications
Respiration Disorders
Fetal Diseases
Pathologic Processes
Respiratory Tract Diseases

Hypertension, Pulmonary
Syndrome
Hernia
Lung Diseases
Hernia, Diaphragmatic
Persistent Fetal Circulation Syndrome
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on September 09, 2009