Endothelial DysfunctionPhase 4NCT00376246
Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects
A Phase 4 study testing Ezetimibe in people with Endothelial Dysfunction, run by University of California, San Diego.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Endothelial Dysfunction
- What is being tested?
- Ezetimibe
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- No sites listed yet
- Study dates
- Sep 2006to Apr 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- healthy adults over 18 yrs of age
Who cannot join
- presence of known metabolic syndrome
- as history of coronary artery disease
- hypertension
- diabetes
- cardiomyopathy
- tobacco use
About this study
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.
Read the 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).
- Conditions
- Endothelial Dysfunction
- Being tested
- Ezetimibe
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EzetimibeDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Other | 1st group will receive Ezetimibe for 2 weeks followed by washout (no medication) period for 4 weeks and followed by placebo for 2 weeks. Receives: Drug: Ezetimibe |
| Group 2 | Other | 2nd group will receive Ezetimibe and placebo in reverse order with interspaced 4-week washout period. Receives: Drug: Ezetimibe |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Flow Mediated Dilation
Measured: before food, 3 hours postprandially and 6 hours postprandially
Secondary outcomes (1)
Lipid Profile- Change in LDL(Low Density Lipoprotein)
Measured: before food, 3 hours post prandial, 6 hours postprandial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2006 (estimated)
- Study startSep 2006
- Primary completionApr 2008
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Endothelial DysfunctionStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ori Ben-Yehuda, University of California, San Diego
- Investigators
- Ori Ben-Yehuda, MD, Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00376246
- Sponsor's protocol ID
- 050714
- Status last verified
- Feb 2020
- First submitted
- 13 Sep 2006
- Last updated
- 12 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00376246
- Acronym / sponsor ID
- 050714
- Conditions
- Endothelial Dysfunction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 14 Sep 2006 (estimated)
- Results
- Posted 12 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Other | Drug: Ezetimibe1st group will receive Ezetimibe for 2 weeks followed by washout (no medication) period for 4 weeks and followed by placebo for 2 weeks. |
| Group 2 | Other | Drug: Ezetimibe2nd group will receive Ezetimibe and placebo in reverse order with interspaced 4-week washout period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- healthy adults over 18 yrs of age
Key exclusion criteria (6 listed)
- presence of known metabolic syndrome
- as history of coronary artery disease
- hypertension
- diabetes
- cardiomyopathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ezetimibe | Drug | Group 1, Group 2 |
Primary outcome
Percent Change in Flow Mediated Dilation
Time frame: before food, 3 hours postprandially and 6 hours postprandially
1 secondary outcome
Lipid Profile- Change in LDL(Low Density Lipoprotein)
Time frame: before food, 3 hours post prandial, 6 hours postprandial
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ori Ben-Yehuda, MD principal investigator
UCSD
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ezetimibe in people with Endothelial Dysfunction, run by University of California, San Diego.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Flow Mediated Dilation (time frame: before food, 3 hours postprandially and 6 hours postprandially). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2020.