Study of the Effect of Innate on the Inflammatory Response to Endotoxin

March 12, 2024 updated by: National Institute of Environmental Health Sciences (NIEHS)

Study of the Effect of Innate Immunity on the Inflammatory Response to Endotoxin

Background:

- Innate immunity is the process by which white blood cells and other parts of the immune system sense and respond to potential infections by causing an inflammation. Researchers are interested in studying how the body responds to certain environmental factors, and whether the body s response can contribute to chronic illnesses or diseases such as asthma and certain types of cancers.

Objectives:

- To examine how specific genes and proteins in blood cells respond to environmental exposures.

Eligibility:

- Healthy volunteers between 18 and 45 years of age.

Design:

  • The study will involve one visit of 45 to 60 minutes.
  • Participants will be screened with a brief physical examination and finger stick to determine if they are eligible to donate blood for the study, and will complete a questionnaire about any medications or other drugs (e.g., cigarettes) they may be taking.
  • Participants will provide a blood sample for research purposes.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This research study will examine the role of innate immunity on the Inflammatory response of monocytes and macrophages to endotoxin. Approximately 1450 healthy participants aged 18 years and older will be identified and recruited from the Environmental Polymorphism Registry (EPR). The EPR is a long-term project to collect and store up to 15,000 DNA samples for use in research studies from individuals in the greater North Carolina Triangle Region. It is anticipated that approximately 50% of the participants contacted will enroll and about 15% of participants enrolled will withdraw.

This controlled, observational gene association study will recruit participants on the basis of genotype and then observe the phenotype of each participant. There are several SNPs of interest in the genes TIRAP, MyD88, ABCA1, CD14, CD44, ITIH3, ITIH4, TLR4, TNFa, TLR5, IRGM, and APOL1. In addition there are alleles of interest in the gene ApoE. These alleles taken together are considered a polymorphism. For each polymorphism of interest a separate group of participants will be recruited (including heterozygous and homozygous for both the minor and major alleles for each SNP). A maximum of 200 mLs of blood will be obtained from each participant during one visit lasting approximately 1-1.5 hours. Blood monocytes will be isolated from the donated blood samples and cultured to obtain macrophages. The macrophages will be exposed ex vivo to an endotoxin (LPS) and to PAM3CSK4 to determine cell response depending on genotype. In studies of APOL1, a urine specimen will also be collected to evaluate for protein filtration.

The primary objective is to determine associations between select polymorphisms in genes [TIRAP (TIR Associated Protein), MyD88 (Myeloid Differentiation Primary Response Protein 88), ApoE (Apolipoprotein E), ABCA1 (ATP Binding Cassette Transporter A1), CD14, CD44, ITIH3, ITIH4, TLR4, TNFa, TLR5, IRGM, and APOL1] and quantitative in vitro inflammatory functions of two cell types, the macrophage and neutrophil. The primary endpoints of this study for both cell types will be levels of 6 cytokines TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA) induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK4). Urinary levels of protein will be quantified in some studies as a measure of early kidney dysfunction.

We hope the results of this study may lead to discovery of important information regarding the role of MDC1 (Mediator of DNA damage Checkpoint protein 1) in human disease, potentially identifying new targets for future studies.

Study Type

Observational

Enrollment (Estimated)

725

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: NIEHS Join A Study Recruitment Group
  • Phone Number: (855) 696-4347
  • Email: myniehs@nih.gov

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Research Triangle Park, North Carolina, United States, 27709
        • Recruiting
        • NIEHS Clinical Research Unit (CRU)
        • Contact:
          • NIEHS Join A Study Recruitment Group
          • Phone Number: 855-696-4347
          • Email: myniehs@nih.gov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants enrolled in Environmental Polymorphism Registry (EPR)@@@

Description

  • INCLUSION CRITERIA:
  • Male or female 18 years of age or older
  • Participants must be able to understand and provide written informed consent to participate in the study
  • Participants must be able to travel to the CRU
  • Willing and able to fast after midnight the night prior to their study appointment
  • Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. If the individual has a chronic condition such as diabetes or high blood pressure, healthy also means that they are being treated and the condition is under control).

EXCLUSION CRITERIA:

  • Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 5 days prior to enrollment visit (e.g., Motrin, ibuprofen, naproxen, and Advil)
  • Use of acetaminophen (Tylenol) within 5 days prior to enrollment visit
  • Use of cholesterol lowering drugs (statins) within 30 days prior to enrollment visit (e.g., Zocor, Mevacor, Lipitor, and Crestor)
  • Use of immunosuppressants or other immune-modifying drugs [e.g., Rituxan, Humira, Enbrel, Cyclosporin (Neoral, Sandimmune, and SangCya), and Azathioprine (Imuran)], Monoclonal antibodies [e.g., infliximab (Remicade)], and corticosteroids (e.g., prednisone, prednisolone and dexamethasone)
  • Current treatment for cancer with chemotherapy or radiation
  • Confirmed or suspected immunosuppressive or immunodeficient condition
  • GI or respiratory Illness within 5 days prior to enrollment visit, including cold or allergies
  • Smoked tobacco, chewed tobacco or used electronic cigarettes within 2 weeks prior to enrollment visit (for participants who provide a urine specimen, this will be defined by urine cotinine >200 ng/mL at visit)
  • Alcohol consumption greater than 2 standard drinks (1 standard drink contains 15 g of ethanol) per day within the last 24 hours prior to the enrollment visit
  • Body weight < 50 kg (<110 lbs)
  • Temperature > 37.6 C; blood pressure < 90/50 mm Hg or > 170/95 mm Hg; pulse rate < 50 or >100 beats/minute
  • Pregnant or suspected pregnancy
  • Chronic Kidney Disease

The PI may review medication use on a case by case basis and make a medical determination on the participant s eligibility. In these cases, the PI determination will be documented in the participant s chart.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
ABCA1
SNP or allele of interest
APOE
SNP or allele of interest
APOL1
SNP or allele of interest
CD14
SNP or allele of interest
CD44
SNP or allele of interest
IRGM
SNP or allele of interest
ITIH3
SNP or allele of interest
ITIH4
SNP or allele of interest
MyD88
SNP or allele of interest
TIRAP
SNP or allele of interest
TLR4
SNP or allele of interest
TLR5
SNP or allele of interest
TNFa
SNP or allele of interest

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary endpoints of this study are for both cell types and will be levels of 6 cytokines [TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA)] induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK...
Time Frame: After analysis
The primary endpoints of this study are for both cell types and will be levels of 6 cytokines [TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA)] induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK4).
After analysis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Environmental Health Sciences (NIEHS)

Investigators

  • Principal Investigator: Michael B Fessler, M.D., National Institute of Environmental Health Sciences (NIEHS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2012

Study Registration Dates

First Submitted

June 11, 2010

First Submitted That Met QC Criteria

June 11, 2010

First Posted (Estimated)

June 14, 2010

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

July 21, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 100129
  • 10-E-0129

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

.It isn t known yet if there will be a plan to make IPD available

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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