Ignite Creation Date:
2024-05-06 @ 1:46 PM
Last Modification Date:
2024-10-26 @ 1:19 PM
Study NCT ID:
NCT04112355
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2023-10-02
First Post:
2019-04-08
Brief Title:
Measuring the Healthy Pediatric Inflammatory Response to Vaccination
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Establishing the Dynamic Range of Healthy Pediatric Inflammatory Responses to Vaccinations and Identifying the Role of IL1RN Polymorphisms in Controlling This Response
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this research is to understand the normal healthy response to immunological challenge by measuring circulating cytokine and chemokine levels before and after vaccinations in healthy children These data will define a range of normal responses that can be used to help us understand pathogenic mechanisms in children who do not respond normally to infections In addition this study will test the hypothesis that genetic polymorphisms in the interleukin-1 receptor antagonist gene are associated with differential inflammatory responses across the healthy spectrum
Detailed Description:
Children who experience seizures that cannot be stopped by traditional anti-seizure medications often suffer profound brain injury and intellectual disability Indeed many of these children do not survive In one study 12 of children who developed an acute onset disease called FIRES febrile infection-related epilepsy syndrome died during the early stages of the disease and of the children who survived more than 90 developed cognitive impairment and lifelong epilepsy that could not be treated by our standard drugs The discovery of new therapeutic strategies is therefore imperative
A role for inflammation and the innate and adaptive immune systems in generating seizures is a burgeoning but understudied field in epilepsy research While data from multiple human and animal studies suggests that inflammatory cytokines can drive ictogenesis the development of strategies to modulate inflammation are hindered by insufficient knowledge regarding the dynamic range of healthy responses to infection and immunological challenge On this basis the investigators intend to measure changes in levels of inflammatory cytokines and chemokines in the blood induced by the normal healthy response to vaccination To do so the investigators will collect a small amount of blood from children just before they receive their standard vaccinations at 6 months 12 months or 4-6 years of age A follow-up sample will then be collected from the same children approximately 10-14 days later Since it is known that about 30 of children develop a fever within this timeframe it is expected that the size of the change in inflammatory factors in each child will reflect a Gaussian distribution with high responders and low responders centered on a mean response For each sample the investigators will isolate serum and measure the levels of interleukin-1 beta interleukin-6 tumor necrosis factor alpha chemokine C-C motif ligand 2 chemokine C-C motif ligand 5 chemokine C-X-C motif ligand 1 chemokine C-X-C motif ligand 2 chemokine C-X-C motif ligand 8 chemokine C-X-C motif ligand 9 and chemokine C-X-C motif ligand 10
In addition based on recent findings showing that some children with acute seizure disorders exhibit previously unknown genetic polymorphisms in the interleukin-1 receptor antagonist IL1RA gene that are associated with altered immunological function the investigators have hypothesized that normal healthy children will exhibit a spectrum of IL1RA function that will correlate with the size of their response to vaccination To test this hypothesis the investigators will collect genomic DNA for sequencing of the IL1RA gene also known as IL1RN and will measure the function of the IL1RA protein in serum This genetic and functional data will be correlated with the inflammatory cytokine and chemokine response measured in serum
Several key findings will be made in this study
1 Measure the normal range of inflammatory responses that occur in the blood when a person is given a vaccine blood will be collected just before the vaccination and then again 1-2 weeks later
2 Measure protein function in the blood and build up a graph showing the range of such function in healthy kids
3 Sequence the gene that produces a specific protein in healthy children All humans have minor changes in genes that subtly alter the function of proteins These are called polymorphisms and they are completely normal The investigators want to build up a picture of the type of polymorphisms that occur in children and then compare these differences This information might help to someday develop new ways to help children with dysfunctional proteins
This study is in no way based on the idea that vaccines are bad This study was designed because children all respond a little differently to vaccines for example some get sore at the injection site some get a low fever some feel more tired than usual and this indicates that the body is responding to the immunization in ways that can be measured The investigators think that the normal healthy response to vaccination will help define a range of responses that can be used to help other children who do not respond normally to infections While this study is focused on a specific protein and on helping children who have defects in this factor these findings will be widely relevant to understanding many diseases of the immune system in children
A role for inflammation and the innate and adaptive immune systems in generating seizures is a burgeoning but understudied field in epilepsy research While data from multiple human and animal studies suggests that inflammatory cytokines can drive ictogenesis the development of strategies to modulate inflammation are hindered by insufficient knowledge regarding the dynamic range of healthy responses to infection and immunological challenge On this basis the investigators intend to measure changes in levels of inflammatory cytokines and chemokines in the blood induced by the normal healthy response to vaccination To do so the investigators will collect a small amount of blood from children just before they receive their standard vaccinations at 6 months 12 months or 4-6 years of age A follow-up sample will then be collected from the same children approximately 10-14 days later Since it is known that about 30 of children develop a fever within this timeframe it is expected that the size of the change in inflammatory factors in each child will reflect a Gaussian distribution with high responders and low responders centered on a mean response For each sample the investigators will isolate serum and measure the levels of interleukin-1 beta interleukin-6 tumor necrosis factor alpha chemokine C-C motif ligand 2 chemokine C-C motif ligand 5 chemokine C-X-C motif ligand 1 chemokine C-X-C motif ligand 2 chemokine C-X-C motif ligand 8 chemokine C-X-C motif ligand 9 and chemokine C-X-C motif ligand 10
In addition based on recent findings showing that some children with acute seizure disorders exhibit previously unknown genetic polymorphisms in the interleukin-1 receptor antagonist IL1RA gene that are associated with altered immunological function the investigators have hypothesized that normal healthy children will exhibit a spectrum of IL1RA function that will correlate with the size of their response to vaccination To test this hypothesis the investigators will collect genomic DNA for sequencing of the IL1RA gene also known as IL1RN and will measure the function of the IL1RA protein in serum This genetic and functional data will be correlated with the inflammatory cytokine and chemokine response measured in serum
Several key findings will be made in this study
1 Measure the normal range of inflammatory responses that occur in the blood when a person is given a vaccine blood will be collected just before the vaccination and then again 1-2 weeks later
2 Measure protein function in the blood and build up a graph showing the range of such function in healthy kids
3 Sequence the gene that produces a specific protein in healthy children All humans have minor changes in genes that subtly alter the function of proteins These are called polymorphisms and they are completely normal The investigators want to build up a picture of the type of polymorphisms that occur in children and then compare these differences This information might help to someday develop new ways to help children with dysfunctional proteins
This study is in no way based on the idea that vaccines are bad This study was designed because children all respond a little differently to vaccines for example some get sore at the injection site some get a low fever some feel more tired than usual and this indicates that the body is responding to the immunization in ways that can be measured The investigators think that the normal healthy response to vaccination will help define a range of responses that can be used to help other children who do not respond normally to infections While this study is focused on a specific protein and on helping children who have defects in this factor these findings will be widely relevant to understanding many diseases of the immune system in children
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None