Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Blood Vessel Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 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:
NCT01524549
First received: February 1, 2012
Last updated: November 11, 2014
Last verified: July 2014
  Purpose

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.

Condition
Endothelial Cell Function

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: The Role of the Functionally Relevant Single Nucleotide Polymorphisms CYP2J2 -50G> T (CYP2J2 7) and EPHX2 9846A> G (EPHX2 K55R) in Human Endothelial Function

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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

Estimated Enrollment: 200
Study Start Date: January 2012
Detailed Description:

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.

  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 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
  • For participants with current daily or chronic use of NSAIDs; unable or unwilling to refrain from taking NSAIDs for 7 days prior to enrollment visit. See Table 2 for a comprehensive list
  • 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)
  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: NCT01524549

Contacts
Contact: Lisa B Murphy (919) 541-9839 murphylb@mail.nih.gov
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
Contact: Lisa Murphy    919-541-9839    murphylb@mail.nih.gov   
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: NCT01524549     History of Changes
Other Study ID Numbers: 120061, 12-E-0061
Study First Received: February 1, 2012
Last Updated: November 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cardiovascular
P450s
Flow-Mediated Dilatation
Brachial Artery Ultrasound
Endothelial Cell Function
Healthy Volunteer
HV

ClinicalTrials.gov processed this record on November 24, 2014