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Effect of Ezetimibe on Flow-Mediated Brachial Artery Reactivity in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by:
University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00376246
First received: September 13, 2006
Last updated: June 2, 2008
Last verified: June 2008
  Purpose

The objective of this study is to show that Ezetimibe will improve endothelial function following high cholesterol meals in healthy subjects by decreasing absorption of cholesterol and thus affecting concentration and composition of remnant-like particles.


Condition Intervention
Endothelial Dysfunction
Drug: Ezetimibe

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Effect of Ezetimibe on Flow-Mediated Brachial Artery Reactivity in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • 1)Flow Mediated dilation

Secondary Outcome Measures:
  • 1)Lipid profile

Estimated Enrollment: 24
Study Start Date: September 2006
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Detailed Description:

24 subjects will be recruited. Exclusion criteria will be presence of known metabolic syndrome as well as history of coronary artery disease, hypertension, diabetes, cardiomyopathy and tobacco use. Study will be conducted as double blind placebo controlled crossover trial. Subjects will be randomized to 2 groups. 1st group will receive Ezetimibe for 2 weeks followed by washout (no medication) period for 4 weeks and followed by placebo for 2 weeks. 2nd group will receive Ezetimibe and placebo in reverse order with interspaced 4-week washout period. Each subject will be evaluated during 2 visits at the ends of the intervention periods (Ezetimibe and placebo). Visits will occur after 2 and 8 weeks after enrollment. Subjects will be asked to fast 12 hrs before each visit. During each visit, a subject will undergo brachial artery reactivity study (BART) before consumption of standardized high cholesterol meal and at 3 and 6-hour points after the meal. The standardized high cholesterol meal will consist of 2 Egg McMuffin® sandwiches. This meal weighs 276 g and contains 34g of protein, 60g of carbohydrates, 22g of total fat and 470 mg of cholesterol and has 290 Calories. Subjects also will have blood draws for serum lipid measurement performed before each BART procedure (total of 3 BART and 3 blood sample collections per patient per visit).

Brachial artery reactivity studies will be conducted per following protocol:

  • Equipment - Echocardiography system w/vascular software for 2-D imaging, Doppler and high-frequency vascular transducer.
  • Initial image - Subject will be placed in a temperature-controlled room (22Cº). With subject positioned supine, left brachial artery will be imaged 5 cm above antecubital crease in longitudinal plane twice. Blood pressure and heart rate will be also measured.
  • FMD - 12.5 cm blood pressure cuff will be placed above the antecubital fossa on left arm, baseline flow velocity will be obtained by pulsed Doppler. Thereafter, artery will be occluded by cuff inflation to 50 mm Hg above systolic pressure for 5 minutes and subsequently deflated. The longitudinal image will be obtained 1 min after cuff release.
  • FMD w/NTG - 10 min after baseline study, FMD with NTG will be obtained. 0.4 mg sublingual NTG tablet will be given to subject and 4 min later, FMD imaging will be repeated as described above.
  • Analysis - Photographic images of end-diastolic frames will be obtained. Images will be analyzed by 2 independent investigators blinded to the subject's identity and temporal sequence of images. Arterial diameter of the brachial artery in longitudinal plane from images where there is clear visualization of anterior and posterior intimal/lumen interface will be determined by caliper measurement. FMD quantified as a percent diameter change of the post-occlusion arterial diameter measurement relative to the mean of the 2 corresponding baseline measurements. Similar analysis will be performed for FMD following administration of NTG.

Lipid testing will be performed using the VAP® test and will include VLDL, LDL, HDL and IDL lipoprotein fractions as well as Triglycerides, Lipoprotein A, CRP and Homocysteine. Statistical analysis will be conducted as follows: group values for percent change in arterial diameter will be expressed as mean +/- SD. 2- tailed paired t-test will be used to compare changes in individual subjects. Two-tailed non-paired t-test will be used to compare values between groups. The analyses for FMD - lipid lowering correlation will be performed using a paired t test for parametrically distributed data and the Wilcoxon matched-pair signed rank test for nonparametrically distributed data to compare baseline data and changes in all variables at the end of the study within each group. The t test will used to compare the baseline characteristics between those receiving ezetimibe and those receiving placebo in all groups. Correlation between variables will be tested using both univariate and multitivariate analyses. The results will be presented as mean ± SD andmedian (25-75 percentiles).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy adults over 18 yrs of age

Exclusion Criteria:

  • presence of known metabolic syndrome
  • as history of coronary artery disease
  • hypertension
  • diabetes
  • cardiomyopathy
  • tobacco use
  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: NCT00376246

Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: Ori Ben-Yehuda, MD UCSD
  More Information

No publications provided

Responsible Party: Ori Ben-Yehuda, MD, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00376246     History of Changes
Other Study ID Numbers: 050714
Study First Received: September 13, 2006
Last Updated: June 2, 2008
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Ezetimibe
Anticholesteremic Agents
Antimetabolites
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014