Ignite Creation Date:
2024-05-05 @ 5:02 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00376246
Status:
COMPLETED
Last Update Posted:
2020-02-12
First Post:
2006-09-13
Brief Title:
Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects
Sponsor:
University of California San Diego
Organization:
University of California San Diego
Study Overview
Official Title:
Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects
Status:
COMPLETED
Status Verified Date:
2020-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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 wvascular 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 - 125 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 wNTG - 10 min after baseline study FMD with NTG will be obtained 04 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 subjects 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 intimallumen 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
Brachial artery reactivity studies will be conducted per following protocol
Equipment - Echocardiography system wvascular 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 - 125 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 wNTG - 10 min after baseline study FMD with NTG will be obtained 04 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 subjects 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 intimallumen 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None