Healthy ControlsNCT04112355
Measuring the Healthy Pediatric Inflammatory Response to Vaccination.
An observational study of Healthy Controls, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 months to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Controls
- What is being tested?
- Blood Collection
- Type of treatment
- Vaccines
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2019to Dec 2028
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 months to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Children scheduled for vaccinations at Mayo Clinic in Rochester, MN
Who may be able to join
- Children 5-7 months of age receiving the 3rd scheduled dose of the diphtheria, tetanus, pertussis, inactivated polio, Haemophilus influenzae type b, and pneumococcal conjugate vaccine (DTap-IPV/Hib+PCV13).
- Children 10-18 months of age receiving the 1st scheduled dose of the measles, mumps, rubella, and varicella vaccine (MMR+VZV).
- Children 4-6 years of age receiving the 2nd scheduled MMR+VZV dose.
- Children and young adults receiving the annual flu vaccine or COVID vaccine
Who cannot join
- History of autoinflammatory or autoimmune disease.
- History of genetic or metabolic disorder.
- History of hematological disorder.
- History of malignancy or active malignancy undergoing suppressive treatment.
- Blood donation or collection within 8 weeks of the study.
- Signs or symptoms consistent with severe infection at the time of first visit.
- Weight less than 6 kg in group 1, less than 7.5 kg for group 2, less than 12 kg for group 3.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Establishing the Dynamic Range of Healthy Pediatric Inflammatory Responses to Vaccinations and Identifying the Role of IL1RN Polymorphisms in Controlling This Response.
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.
Read the 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.
- 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.
- Measure protein function in the blood and build up a graph showing the range of such function in healthy kids.
- 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.
- Conditions
- Healthy Controls
- Being tested
- Blood Collection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood CollectionOther
Blood draw
| Study group | Role | What they receive |
|---|---|---|
| 6 months of age | Visit 1
This visit will take about 15 minutes and will be at the time of the next scheduled clinical vaccinations. Study procedures at this visit include :
* Draw a blood sample based on age groups below
* Provided a temperature diary to fill out for the next week Visit 2
This visit will take about 15 minutes and will be approximately 7 days after the first visit. Study procedures at this visit include :
* Draw a blood sample based on age groups below
* Collect temperature diary if not already mailed in Receives: Other: Blood Collection | |
| 12 months of age | Visit 1
This visit will take about 15 minutes and will be at the time of the next scheduled clinical vaccinations. Study procedures at this visit include :
* Draw a blood sample based on age groups below
* Provide a temperature diary to fill out for the next week Visit 2
This visit will take about 15 minutes and will be approximately 7 days after the first visit. Study procedures at this visit include :
* Draw a blood sample based on age groups below
* Collect temperature diary if not already mailed in Receives: Other: Blood Collection | |
| 5 years of age | Visit 1
This visit will take about 15 minutes and will be at the time of the next scheduled clinical vaccinations. Study procedures at this visit include :
* Draw a blood sample based on age groups below
* Provide a temperature diary to fill out for the next week Visit 2
This visit will take about 15 minutes and will be approximately 7 days after the first visit. Study procedures at this visit include :
* Draw a blood sample based on age groups below
* Collect temperature diary if not already mailed in Receives: Other: Blood Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in normal pediatric interleukin-1 beta levels in serum at 1 week after immunization relative to baseline.
Measurement of serum interleukin-1 beta levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric interleukin-6 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum interleukin-6 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric tumor necrosis factor-alpha levels in serum at 1 week after immunization relative to baseline.
Measurement of serum tumor necrosis factor-alpha levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric chemokine (C-C motif) ligand 2 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum chemokine (C-C motif) ligand 2 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric chemokine (C-C motif) ligand 5 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum chemokine (C-C motif) ligand 5 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric chemokine (C-X-C motif) ligand 1 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum chemokine (C-X-C motif) ligand 1 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric chemokine (C-X-C motif) ligand 2 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum chemokine (C-X-C motif) ligand 2 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric chemokine (C-X-C motif) ligand 8 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum chemokine (C-X-C motif) ligand 8 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric chemokine (C-X-C motif) ligand 9 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum chemokine (C-X-C motif) ligand 9 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Changes in normal pediatric chemokine (C-X-C motif) ligand 10 levels in serum at 1 week after immunization relative to baseline.
Measurement of serum chemokine (C-X-C motif) ligand 10 levels will be analyzed and compared between the pre-immunization and post-immunization timepoints. Response profiles will also be compared between subjects.
Measured: Baseline, 1week
Determine the range of normal single nucleotide polymorphisms in the interleukin-1 receptor antagonist (IL-1RN) gene.
The IL-1RN gene will be sequenced from genomic DNA. Sequences will be compared between subjects and associated with cytokine and chemokine levels.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start16 Aug 2019
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ControlsStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles L. Howe, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04112355
- Sponsor's protocol ID
- 19-001219
- Status last verified
- Jan 2026
- First submitted
- 8 Apr 2019
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No