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The COX-2 Gene and the Immune System

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Environmental Health Sciences (NIEHS) )
ClinicalTrials.gov Identifier:
NCT01678222
First received: August 30, 2012
Last updated: November 11, 2014
Last verified: March 2014
  Purpose

Background:

- The immune system contains several different types of cells in the blood and other parts of the body. The body can fight infections well with the right balance of these cell types. The wrong balance of cell types may cause diseases, such as allergies or asthma. The COX-2 gene may help decide the balance of cell types that the body makes as part of the immune system. It may also play a role in certain immune system diseases. Researchers want to see how COX-2 affects the cells in the immune system.

Objectives:

- To study how the COX-2 gene works in the body s immune system.

Eligibility:

- Individuals between 18 and 65 years of age who are part of the Environmental Polymorphisms Registry.

Design:

  • Participants will have one study visit at the National Institutes of Health. They will collect a urine sample at home on the morning of the study visit.
  • Participants will have a physical exam and medical history. They will provide a blood sample. They will also give researchers the urine sample they collected that morning.
  • No treatment will be provided as part of this study.

Condition
Cyclooxygenase-2
Lymphocyte
Eicosanoid
Prostaglandin

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Role of Functionally Relevant Cyclooxygenase-2 (COX-2) Gene Single Nucleotide Polymorphisms -765G> C and 8473T> C in Lymphocyte Differentiation

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine whether 765& gt; C is associated with altered Th2, Th9, and Th17 differentiation in vivo

Secondary Outcome Measures:
  • To determine whether 8473T& gt; C is associated with altered Th2, Th9, and Th17 differentiation in vivo
  • To determine whether 765G& gt; C is associated with altered prostaglandin and cytokine levels in vivo

Estimated Enrollment: 93
Study Start Date: August 2012
Detailed Description:

This is a cross-sectional, controlled study designed to investigate the association of single nucleotide polymorphisms (SNPs) in the cyclooxygenase-2 (COX2) gene, also called prostaglandin endoperoxidase synthase 2 (PTGS2), on T-cell differentiation and function. Specifically, the impact of the promoter-region SNP 765G> C (rs20417) and the 3 untranslated region (UTR) SNP 8473T> C (rs5275) on T helper cell (Th) 2, Th9, and Th17 differentiation and function will be examined. Non-Hispanic, White or Black/African American, non-pregnant adults, aged 18-65 years, who are wild type (WT), with respect to both the 765G> C and 8473T> C SNPs, WT with respect to 765G> C and homozygous for 8473T> C, and homozygous for both 765G> C and 8473T> C will be recruited into a total of three genotype groups. A group of individuals who are homozygous for -765G> C and WT with respect to 8473T> C are extremely rare and will be recruited if any participants with this SNP combination are found in the participant pool. Potential participants will be identified from the Environmental Polymorphisms Registry, contacted and pre-screened for eligibility. Pre-screened individuals will provide verbal consent to withhold certain supplements/medications prior to the study visit, and will be mailed an informed consent form, a urine collection cup, and pre-visit instructions. Participants will attend a single study visit that will take place at the National Institute of Environmental Health Sciences (NIEHS) Clinical Research Unit (CRU). During this visit, written informed consent will be obtained, and there will be a final screening and eligibility determination, medical history review, vital signs, physical examination and blood and urine samples will be collected. From peripheral blood, lymphocyte subsets, prostaglandin levels, and cytokine levels will be determined; stable prostaglandin metabolites, creatinine, total protein and albumin will be measured in urine. Lymphocytes will be isolated from peripheral blood for ex vivo analyses. Demographic characteristics (i.e., age) will be compared between the groups, and when possible, recruitment will be targeted to achieve an approximate match of race and gender across the groups. The primary objective of the study is to determine whether the 765G> C or 8473T> C SNPs exhibit altered Th2, Th9 and Th17 cell differentiation by examining lymphocyte subsets in vivo. The study will also examine the impact of these two SNPs on circulating Th2/Th9/Th17 cytokine levels and prostaglandins in vivo, on differentiation of naive CD4+T-cells to Th cell subsets in vitro, and on lymphocyte production of cytokines and prostaglandins in vitro.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Participant of the Environmental Polymorphisms Registry and current contact information available
  • Genotype information available for relevant 765G> C and 8473T> C COX2 polymorphisms, which indicates:

    • Individuals who are WT with respect to both 765G> C and 8473T> C (N=31)
    • Individuals who are WT with respect to 765G> C and homozygous for 8473T> C (N=31)
    • Individuals who are homozygous for both 765G> C and 8473T> C (N=31)
    • Individuals who are homozygous for -765G> C and WT with respect to 8473T> C
  • Age 18- 65 years
  • Race self-identified as White or Black and Non-Hispanic ethnicity
  • Willing and able to provide informed consent
  • Able to comply with all protocol procedures

EXCLUSION CRITERIA:

  • History of infection within the preceding 1 week or an oral temperature > 38 (Infinite)C
  • Current daily or chronic use of corticosteroids (systemic and topical.
  • Any current conditions known to impact peripheral white blood cell count (e.g., leukemia, lymphopenia, AIDS, other immunodeficiency disorders)
  • Current daily or chronic use of systemic immunosuppressants.
  • Current pregnancy or lactation
  • Unwilling or unable to:

    • Fast (including alcohol and caffeine-containing products) and discontinue tobacco use for 12 hours prior to the study visit
    • Withhold all prescribed and over-the-counter medications and supplements the morning of the study visit, until after the visit is completed
    • Refrain from taking the following as needed medications and supplements for 7 days prior to the study visit:

      • NSAIDs
      • Corticosteroids (nasal, inhaled, topical or systemic)
      • Fish oil and niacin supplements
  • For blood draws that exceed 200ml, a hematocrit of < 34% for women or < 36% for men, or > 56% for either gender.
  • For blood draws exceeding 200ml, blood or plasma donation in the last 8 weeks
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678222

Contacts
Contact: Darryl C Zeldin, M.D. (919) 541-1169 zeldin@niehs.nih.gov

Locations
United States, North Carolina
NIEHS Clinical Research Unit (CRU) Recruiting
Research Triangle Park, North Carolina, United States
Sponsors and Collaborators
Investigators
Principal Investigator: Darryl C Zeldin, M.D. National Institute of Environmental Health Sciences (NIEHS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Environmental Health Sciences (NIEHS) )
ClinicalTrials.gov Identifier: NCT01678222     History of Changes
Other Study ID Numbers: 120190, 12-E-0190
Study First Received: August 30, 2012
Last Updated: November 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Lymphocyte
Cyclooxygenase 2
Eicosanoid
Prostaglandin

ClinicalTrials.gov processed this record on November 20, 2014