- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00376246
Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects
Study Overview
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).
Study Type
Enrollment (Actual)
Phase
- Phase 4
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Group 1
1st group will receive Ezetimibe for 2 weeks followed by washout (no medication) period for 4 weeks and followed by placebo for 2 weeks.
|
|
Other: Group 2
2nd group will receive Ezetimibe and placebo in reverse order with interspaced 4-week washout period.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percent Change in Flow Mediated Dilation
Time Frame: before food, 3 hours postprandially and 6 hours postprandially
|
before food, 3 hours postprandially and 6 hours postprandially
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Lipid Profile- Change in LDL(Low Density Lipoprotein)
Time Frame: before food, 3 hours post prandial, 6 hours postprandial
|
before food, 3 hours post prandial, 6 hours postprandial
|
Collaborators and Investigators
Investigators
- Principal Investigator: Ori Ben-Yehuda, MD, UCSD
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 050714
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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