Blood Vessel Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01524549
First received: February 1, 2012
Last updated: August 20, 2014
Last verified: August 2013

February 1, 2012
August 20, 2014
January 2012
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Flow-mediated dilation (FMD; endothelium-dependent vasodilation), defined as the peak percent change in brachial artery diameter, relative to baseline, after reactive hyperemia, as measured by ultrasound
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Complete list of historical versions of study NCT01524549 on ClinicalTrials.gov Archive Site
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Blood Vessel Study
The Role of the Functionally Relevant Single Nucleotide Polymorphisms CYP2J2 -50G> T (CYP2J2 7) and EPHX2 9846A> G (EPHX2 K55R) in Human Endothelial Function

Background:

- The endothelium is the inner lining of blood vessels. The cells in this lining help regulate blood flow and immune system function. Problems with endothelial cells can contribute to heart disease, high blood pressure, and diabetes. Certain genes or parts of genes may be related to problems with endothelial function. Researchers want to study healthy adults who have genes that may affect their endothelial function. More information on these genes may provide more information on genetic risk for certain diseases.

Objectives:

- To study healthy adults who have genetic markers related to endothelial cell problems.

Eligibility:

  • Healthy volunteers between 18 and 65 years of age.
  • Current participants of the Environmental Polymorphisms Registry and have certain genes related to endothelial cell problems.

Design:

  • Participants will have a single study visit to collect information and samples.
  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
  • Participants will have an ultrasound of the artery in the arm and will be given a short-acting medication called nitroglycerin to study blood flow and blood pressure.

This is a cross-sectional, controlled study designed to investigate the association of two single nucleotide polymorphisms (SNPs) - a cytochrome P450 (CYP) epoxygenase gene CYP2J2 SNP, CYP2J2 7, and a soluble epoxide hydrolase (sEH) gene EPHX2 SNP encoding a K55R variant with altered endothelial function in humans. Healthy adults, aged 18-65 years, who are either carriers of CYP2J2 7 or EPHX2 K55R, or who are wild type (WT) with respect to either SNP will be recruited into a total of five genotype groups. Potential participants will be identified from the Environmental Polymorphisms Registry, mailed an informational letter, contacted by phone and/or email, and pre-screened for eligibility. As participants are recruited, demographic characteristics (i.e., age, gender, and race/ethnicity) will be compared between the groups, and, if necessary, recruitment will be targeted to achieve an approximate match in demographic characteristics across the groups. Pre-screened individuals will provide verbal consent to refrain from taking certain as needed supplements/medications that could alter endothelial function and recreational drugs (such as marijuana, cocaine and amphetamines) 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 NIEHS Clinical Research Unit. During this visit, written informed consent will be obtained, and there will be a final screening and eligibility determination including medical history review, assessment of vital signs, physical examination, carbon monoxide measurement, pregnancy test (if applicable), and electrocardiogram (ECG). In eligible participants, a lipid panel will be performed and endothelial function will be assessed non-invasively by brachial artery ultrasound (i.e., flow-mediated dilation) and digital peripheral arterial tonometry. Blood and urine (first void) samples will be collected for biomarker analyses, which will be conducted in the Zeldin laboratory at NIEHS. The primary objective of the study is to determine whether individuals who are homozygous or heterozygous for the CYP2J2 7 or EPHX2 K55R SNPs exhibit altered endothelial function compared with individuals who are WT for that SNP. As a secondary objective, the impact of these two SNPs on inflammatory and CYP epoxygenase pathway biomarkers will be examined.

Observational
Time Perspective: Cross-Sectional
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Endothelial Cell Function
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
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  • INCLUSION CRITERIA:
  • Participant of the Environmental Polymorphisms Registry and current contact information available
  • Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates:

    • WT for EPHX2 K55R and WT for CYP2J2 7
    • WT for EPHX2 K55R and heterozygous for CYP2J2 7
    • WT for EPHX2 K55R and homozygous for CYP2J2 7
    • WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30)
    • WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30)
  • Age 18-65 years
  • Willing and able to provide informed consent
  • Able to comply with all protocol procedures

EXCLUSION CRITERIA:

  • Currently pregnant or breast feeding
  • Hospitalized for a cardiovascular disease or stroke event within the previous 3 months
  • Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate)
  • Current use of medications taken for hypertension. See Table 2 for a comprehensive list
  • Current daily or chronic use of NSAIDs
  • Current use of insulin
  • Presence of a pacemaker or implanted cardioverter-defibrillator
  • Presence of an irregular heart rhythm (atrial fibrillation) at the study visit
  • Current resting heart rate < 40 or > 125 beats per minute
  • Current systolic blood pressure < 90 or > 180 mmHg, or diastolic blood pressure > 110 mmHg
  • Skin sensitivity precluding use of ECG electrodes
  • History of hypersensitivity to nitroglycerin or other nitrates or nitrites
  • History of infection within the preceding 1 week or temperature > 38 degrees C
  • Unwilling or unable to:

    • Fast (including alcohol and caffeine-containing products) and discontinue tobacco use for 12 hours prior to Visit 1
    • Withhold all prescribed and over-the-counter medications and supplements the morning of Visit 1, until after the visit is completed
    • Refrain from taking the following, as needed, medications for 7 days prior to Visit 1:

      • Vasoactive agents, such as decongestants (e.g., pseudoephedrine)
      • Recreational drugs such as marijuana, cocaine, and amphetamines
      • Anti-inflammatory agents, such as ibuprofen, naproxen or aspirin
      • Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)
Both
18 Years to 65 Years
No
Contact: Lisa B Murphy (919) 541-9839 murphylb@mail.nih.gov
Contact: Darryl C Zeldin, M.D. (919) 541-1169 zeldin@niehs.nih.gov
United States
 
NCT01524549
120061, 12-E-0061
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National Institute of Environmental Health Sciences (NIEHS)
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Principal Investigator: Darryl C Zeldin, M.D. National Institute of Environmental Health Sciences (NIEHS)
National Institutes of Health Clinical Center (CC)
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP