Immunologic Deficiency Syndromes Clinical Trial
Official title:
Novel Mechanisms and Approaches to Treat Neonatal Sepsis: Adjuvant Therapies, Host Microbiome, and Genomic Expression and Functional Capacity of Innate Immune Cells
Verified date | February 2023 |
Source | University of Florida |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Completed |
Enrollment | 142 |
Est. completion date | October 21, 2022 |
Est. primary completion date | October 21, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | N/A to 55 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | UF Health | Gainesville | Florida |
Lead Sponsor | Collaborator |
---|---|
University of Florida | National Institute of General Medical Sciences (NIGMS), Surgical Infection Society |
United States,
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* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Genomic analysis | The genomic profile will be interpreted using Ingenuity Pathway Analysis (IPA) software to make functional predictions. Additionally, a cytokine analysis, and an evaluation for the prevalence of myeloid derived suppressor cells (MDSCs) that have been shown to correlate with poorer outcomes in adult sepsis studies will be performed. | Day 1 | |
Primary | Functional immunologic analysis | Functional capacity will be confirmed directly by observing chemotaxis and quantifying generation of reactive oxygen species (ROS), rate of phagocytosis, and bacterial killing ability. Additionally, a cytokine analysis, and an evaluation for the prevalence of myeloid derived suppressor cells (MDSCs) that have been shown to correlate with poorer outcomes in adult sepsis studies will be performed. | Day 1 | |
Secondary | Immune Function Correlation with Clinical Outcomes | The clinical course of these neonates will be followed for incidence of infectious complications including sepsis as evident by culture results. Therefore, allowing the investigators to determine if immunologic deficits present at birth correlate with clinical outcomes. | 90 days | |
Secondary | Ex-vivo Adjuvant Therapies On Immune Function | The implementation of adjuvants in both murine and human models has shown improved function of immune effector cells as well as in clinical outcomes. Adjuvant treatment of mice with TLR agonists stimulates polymorphonuclear leukocytes (PMN) recruitment and function, decreases rates of bacteremia, and increases survival to polymicrobial and gram negative sepsis. Vaccination with Bacillus Calmette-Guerin (BCG) at birth reduces mortality by 40% in LBW infants to sepsis (not tuberculosis) in sub-Saharan Africa. Utilizing an ex-vivo design we will evaluate the changes in immune cell functional capacity. | Day 1 | |
Secondary | Ex-vivo Adjuvant Therapies Effect On Immune Cell Genomic Expression | The implementation of adjuvants in both murine and human models has shown improved function of immune effector cells as well as in clinical outcomes. Adjuvant treatment of mice with TLR agonists stimulates polymorphonuclear leukocytes (PMN) recruitment and function, decreases rates of bacteremia, and increases survival to polymicrobial and gram negative sepsis. Vaccination with Bacillus Calmette-Guerin (BCG) at birth reduces mortality by 40% in LBW infants to sepsis (not tuberculosis) in sub-Saharan Africa. Utilizing an ex-vivo design we will evaluate the changes in immune cell genomic expression. | Day 1 | |
Secondary | Microbiome Influences Immune Cell Function | Correlated immune deficiencies with differences in the microbiome at the time of birth will be documented by using microbiomic differences present at the time of birth in term vs preterm neonates using Illumina 16s rRNA technology. This system uses highly conserved sequences among bacteria to identify and classify bacterium. The software then provides taxonomic classification to find a microbiomic signature that is specific to immune dysfunction. | Day 1 |
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