Metabolic SyndromePhase 4PANACEANCT00817843
The PostprAndial eNdothelial Function After Combination of Ezetimibe and simvAstatin Study
A Phase 4 study testing Simvastatin and Simvastatin/Ezetimibe in people with Metabolic Syndrome, run by dr.Frank L.J. Visseren at 5 sites in 2 countries.
Trial summary
The purpose of this study is to investigate whether low-dose simvastatin in combination with ezetimibe in comparison to high-dose simvastatin alone, has a beneficial effect on the function of the endothelium after an oral fat load in patients with metabolic syndrome. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Metabolic Syndrome
- What is being tested?
- Simvastatin and Simvastatin/Ezetimibe
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Apr 2009to Sep 2010
- 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 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has a diagnosis of metabolic syndrome according to the modified 2005 AHA/NHLBI Scientific Statement with at least:
- Abdominal obesity defined as:
- Males: waist circumference >102cm
- Females: waist circumference >88cm and two of the following 4 other criteria:
- Triglycerides>150 mg/dL
- HDL Cholesterol
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- Males: HDL-C<40 mg/dL
- Females:HDL-C<50 mg/dL - Blood pressure
- Systolic Blood Pressure ≥130 mmHg or
- Diastolic Blood Pressure ≥85 mmHg
- Fasting glucose ≥ 100 mg/dL
- Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
- Patient is a male or female of 18-79 years of age on the day of signing informed consent.
- Patient is a non-smoker.
- Patient is willing to maintain a stable diet for the duration of the study.
- Patient is a postmenopausal female who is not receiving hormone therapy (including cyclic and non-cyclical hormone replacement therapy or any estrogen antagonist/agonist). Postmenopausal status is defined as (1) no menses for ≥1 year but <3 years and confirmed by FSH levels elevated into the postmenopausal range (as defined by the designated laboratory) or (2) no menses for at least 3 years.
- Patient is naïve to lipid-lowering therapy. Naïve is defined as not being treated with a statin, a fibrate or ezetimibe for 3 months before Visit 1 (Week -2)
- Patient has a baseline fasting LDL-C level of ≥ 100 mg/dL and < 220 mg/dL, and TG level < 400 mg/dL.
Who cannot join
- Patient has a BMI > 35.
- Patient has hypersensitivity or intolerance to ezetimibe or simvastatin or any component of these medications, or to latex.
- Patient routinely consumes more than 14 alcoholic drinks per week.
- Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
- Patient has a smoking history > 10 pack-years (1 pack-year = at least 20 cigarettes per day for a year) OR patient who has smoked within 3 months prior to Visit 1 (Week -2).
- Patient has exclusionary laboratory values at Visit 1 (Week -2) as listed in the table below:
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- liver transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) > 1.5 X ULN with no active liver disease Serum glucose > 7.0 mmol/L Creatine kinase(CK)> 2 X ULN Albumin:creatinine ratio > 34 TSH <0.3 mcIU/mL or > 5.0 mcIU/mL
- Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
- It is not possible to obtain a FMD measurement of sufficient quality at screening (Visit 1)
- Patient has congestive heart failure, atherosclerotic vascular disease or acute or chronic coronary heart disease.
- 13. Patient has had a partial ileal bypass, gastric bypass, gastric banding, celiac disease or other significant intestinal malabsorption.
- 15. Patient has untreated and uncontrolled hypertension with systolic blood pressure >160 mm Hg or diastolic >100 mm Hg at Visit 1 (Week -2). (Patients with untreated hypertension and with office BP at Visit 1 and Visit 2 averaging 160/100 or less can be enrolled). Patients using blood pressure-lowering medication are excluded.
- 16. Patient has estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 based on the 4-variable MDRD
- 17. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins at Visit 1 (Week -2).
- 18. Patient has diabetes mellitus defined as a history of diabetes or fasting serum glucose > 126 mg/dL.
- For the full exclusion criteria, please check the protocol
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Netherlands4 sites
Academic Medical Center
Amsterdam, 1005 AZ
Vascular Research Center Hoorn
Hoorn, 1624 NP
Department of Vascular Medicine UMC Utrecht
Utrecht, Utrecht, 3584 CX
Tweesteden Ziekenhuis
Waalwijk, 5141 BM
About this study
Official title: Multicenter,Double Blind,Randomized, 2-period, Crossover Study to Compare Ezetimibe/Simvastatin (10mg/10 mg) Combination Tablet Versus Simvastatin 80mg Tablet on Postprandial Arterial Endothelial Function in Patients With Metabolic Syndrome
The purpose of this study is to investigate whether low-dose simvastatin in combination with ezetimibe in comparison to high-dose simvastatin alone, has a beneficial effect on the function of the endothelium after an oral fat load in patients with metabolic syndrome.
Read the detailed description
Metabolic syndrome is defined as a group of cardiovascular risk factors and is mainly driven by the epidemic of obesity. High blood lipid levels after a meal may be an important risk factor for cardiovascular disease. In this study we will investigate whether simvastatin in combination with ezetimibe vs. simvastatin alone, has a beneficial effect on the lipid levels after a meal, but more importantly, whether we can measure a difference in function of the endothelium. In a small pilot study we already found that the combination had a beneficial effect in comparison with simvastatin alone. Now we want to solidify these findings in a larger study.
- Conditions
- Metabolic Syndrome
- Being tested
- Simvastatin, Simvastatin/Ezetimibe
- Keywords
- Postprandial hypertriglyceridemia, Metabolic syndrome, Endothelial function, Flow mediated dilatation, EndoPAT, Simvastatin, Ezetimibe
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called Simvastatin (Zocor)
6 weeks of treatment with simvastatin 80 mg
Simvastatin/EzetimibeDrug
Also called Simvastatin/Ezetimibe (Zetia)
6 weeks of treatment with simvastatin 10 mg / ezetimibe 10 mg combination
| Study group | Role | What they receive |
|---|---|---|
| First Simva 80mg then Simvai/Eze10/10mg | Experimental | First 6 weeks of Simvastatin 80mg, then 6 weeks of Simvastatin/Ezetimibe 10/10mg after 6 weeks of placebo washout Receives: Drug: Simvastatin; Drug: Simvastatin/Ezetimibe |
| First Simva/Eze 10/10mg then Simva 80mg | Experimental | First 6 weeks of Simvastatin/Ezetimibe 10/10mg, then 6 weeks of Simvastatin 80mg after 6 weeks of placebo washout Receives: Drug: Simvastatin; Drug: Simvastatin/Ezetimibe |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Difference in (Postprandial-Fasting) FMD
A comparison of the postprandial minus fasting change in FMD under treatment with simvastatin 80 mg versus simvastatin 10/10 mg
Measured: After 6 weeks of treatment
Secondary outcomes (3)
Postprandial Endopat Measurement
Measured: after 6 weeks of treatment (crossover)
Preprandial Endothelial Function Measured by FMD
Measured: after 6 weeks of treatment (crossover)
Preprandial Endopat Measurement
Measured: after 6 weeks of treatment (crossover)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2009 (estimated)
- Study startApr 2009
- Primary completionSep 2010
- Study completionSep 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- dr.Frank L.J. Visseren
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, dr.Frank L.J. Visseren, UMC Utrecht
- Investigators
- Frank LJ Visseren, MD PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817843
- Sponsor's protocol ID
- Vasc-UMCU-10B
- Other IDs
- 2008-003908-61, 2008
- Acronym
- PANACEA
- Status last verified
- Jan 2013
- First submitted
- 6 Jan 2009
- Last updated
- 9 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Olijhoek JK, Hajer GR, van der Graaf Y, Dallinga-Thie GM, Visseren FL. The effects of low-dose simvastatin and ezetimibe compared to high-dose simvastatin alone on post-fat load endothelial function in patients with metabolic syndrome: a randomized double-blind crossover trial. J Cardiovasc Pharmacol. 2008 Aug;52(2):145-50. doi: 10.1097/FJC.0b013e31817ffe76.
PubMed 18670365
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter,Double Blind,Randomized, 2-period, Crossover Study to Compare Ezetimibe/Simvastatin (10mg/10 mg) Combination Tablet Versus Simvastatin 80mg Tablet on Postprandial Arterial Endothelial Function in Patients With Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT00817843
- Acronym / sponsor ID
- PANACEA / Vasc-UMCU-10B
- Conditions
- Metabolic Syndrome
- Keywords
- Postprandial hypertriglyceridemia, Metabolic syndrome, Endothelial function, Flow mediated dilatation, EndoPAT, Simvastatin, Ezetimibe
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- dr.Frank L.J. VisserenUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Apr 2009
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 7 Jan 2009 (estimated)
- Results
- Posted 9 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate whether low-dose simvastatin in combination with ezetimibe in comparison to high-dose simvastatin alone, has a beneficial effect on the function of the endothelium after an oral fat load in patients with metabolic syndrome.
Detailed description
Metabolic syndrome is defined as a group of cardiovascular risk factors and is mainly driven by the epidemic of obesity. High blood lipid levels after a meal may be an important risk factor for cardiovascular disease. In this study we will investigate whether simvastatin in combination with ezetimibe vs. simvastatin alone, has a beneficial effect on the lipid levels after a meal, but more importantly, whether we can measure a difference in function of the endothelium. In a small pilot study we already found that the combination had a beneficial effect in comparison with simvastatin alone. Now we want to solidify these findings in a larger study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| First Simva 80mg then Simvai/Eze10/10mg | Experimental | Drug: Simvastatin, Drug: Simvastatin/EzetimibeFirst 6 weeks of Simvastatin 80mg, then 6 weeks of Simvastatin/Ezetimibe 10/10mg after 6 weeks of placebo washout |
| First Simva/Eze 10/10mg then Simva 80mg | Experimental | Drug: Simvastatin, Drug: Simvastatin/EzetimibeFirst 6 weeks of Simvastatin/Ezetimibe 10/10mg, then 6 weeks of Simvastatin 80mg after 6 weeks of placebo washout |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient has a diagnosis of metabolic syndrome according to the modified 2005 AHA/NHLBI Scientific Statement with at least:
- Males: waist circumference >102cm
- Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
- Patient is a male or female of 18-79 years of age on the day of signing informed consent.
- Patient is a non-smoker.
Key exclusion criteria (16 listed)
- Patient has a BMI > 35.
- Patient has hypersensitivity or intolerance to ezetimibe or simvastatin or any component of these medications, or to latex.
- Patient routinely consumes more than 14 alcoholic drinks per week.
- Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
- Patient has a smoking history > 10 pack-years (1 pack-year = at least 20 cigarettes per day for a year) OR patient who has smoked within 3 months prior to Visit 1 (Week -2).
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 |
|---|---|---|
| SimvastatinAlso: Simvastatin (Zocor)6 weeks of treatment with simvastatin 80 mg | Drug | First Simva 80mg then Simvai/Eze10/10mg, First Simva/Eze 10/10mg then Simva 80mg |
| Simvastatin/EzetimibeAlso: Simvastatin/Ezetimibe (Zetia)6 weeks of treatment with simvastatin 10 mg / ezetimibe 10 mg combination | Drug | First Simva 80mg then Simvai/Eze10/10mg, First Simva/Eze 10/10mg then Simva 80mg |
Primary outcome
Treatment Difference in (Postprandial-Fasting) FMD
Time frame: After 6 weeks of treatment
A comparison of the postprandial minus fasting change in FMD under treatment with simvastatin 80 mg versus simvastatin 10/10 mg
3 secondary outcomes
Postprandial Endopat Measurement
Time frame: after 6 weeks of treatment (crossover)
Preprandial Endothelial Function Measured by FMD
Time frame: after 6 weeks of treatment (crossover)
Preprandial Endopat Measurement
Time frame: after 6 weeks of treatment (crossover)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18670365Olijhoek JK, Hajer GR, van der Graaf Y, Dallinga-Thie GM, Visseren FL. The effects of low-dose simvastatin and ezetimibe compared to high-dose simvastatin alone on post-fat load endothelial function in patients with metabolic syndrome: a randomized double-blind crossover trial. J Cardiovasc Pharmacol. 2008 Aug;52(2):145-50. doi: 10.1097/FJC.0b013e31817ffe76.
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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.
Frank LJ Visseren, MD PhD principal investigator
UMC Utrecht
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simvastatin and Simvastatin/Ezetimibe in people with Metabolic Syndrome, run by dr.Frank L.J. Visseren at 5 sites in 2 countries.
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 18 inclusion and 16 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 9 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
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 9 Jan 2013). 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?
Treatment Difference in (Postprandial-Fasting) FMD (time frame: After 6 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00817843, which also lists 1 linked publication.
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 9 Jan 2013.