InflammationPhase 4NCT04638400
Anti-inflammatory Effects of Simvastatin
A Phase 4 study testing Simvastatin 40mg and Ezetimibe 10mg in people with Inflammation and Atherosclerosis, run by paresh Dandona at 1 site in United States.
Trial summary
The purpose of this research study is to determine which of the two ingredients of Vytorin (Simvastatin or Ezetimibe) is responsible for the anti-inflammatory effects of Vytorin Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammation, Atherosclerosis, Hypercholesterolemia
- What is being tested?
- Simvastatin 40mg and Ezetimibe 10mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2017to 1 Nov 2021
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age: 18 to 75 years of age.
- Obese (BMI ≥30 kg/m2)
- LDL cholesterol of ≥100 mg/dl
- Not taking any vitamins or antioxidants
Who cannot join
- Currently using anti-hyperlipidemic therapies
- Triglycerides >500 mg/dl.
- Myocardial infarction, angioplasty/stent placement or coronary artery bypass surgery in the past 6 months.
- Patient on chronic use of non-steroidal anti-inflammatory drugs or steroids
- Hepatic disease
- Renal impairment.
Show all 13Show fewer
- History of drug or alcohol abuse
- Participation in any other concurrent clinical trial
- Use of an investigational agent or therapeutic regimen within 30 days of study.
- Smoker
- Pregnancy
- Premenopausal women who are not on birth control pills and have not had a hysterectomy or tubal ligation
- Anemia with hemoglobin <12 g/dl
Trial locations and contacts
1 site in 1 country.
United States1 site
Diabetes and Endocrinology Research Center of WNY
Buffalo, New York, 14221
About this study
Official title: Comparison of Effects of Simvastatin Versus Ezetimibe on Intracellular Lipid and Inflammation in Obese Subjects
The purpose of this research study is to determine which of the two ingredients of Vytorin (Simvastatin or Ezetimibe) is responsible for the anti-inflammatory effects of Vytorin
Read the detailed description
Cardiovascular disease is currently the leading cause of death in the developed countries. Atherosclerosis is the most important cause of cardiovascular disease. Statins are known to exert a powerful anti-atherogenic action which is reflected in a marked beneficial effect on the prevention of cardiovascular effects and cardiovascular mortality. They induce a reduction in the progression and an increase in the regression of atherosclerotic lesions. Statins exert powerful effect on lowering LDLc and are also anti-inflammatory due to their ability to lower CRP concentrations. But little is known about their anti-inflammatory effects at a cellular and molecular levels in humans, in vivo.
Vytorin, a preparation containing simvastatin and ezetimibe, has a powerful effect on lowering LDLc concentration through a combination of effects on the absorption of cholesterol from the gut and hepatic cholesterol biosynthesis. In our previous study we have shown that Vytorin exerts a potent anti-inflammatory effect in the obese in the fasting state and following acute inflammatory changes induced by the intake of cream. The IMPROVE-IT trial, which examined the benefits of adding ezetimibe to simvastatin, showed a small additional benefit of ezetimibe (a 6% reduction in cardiovascular events) compared to simvastatin alone. This is marginal when compared to the established cardiovascular benefits of statins.
We, therefore, explore further into the anti-inflammatory actions of the two components of Vytorin by comparing the effects of simvastatin versus ezetimibe on intracellular lipid and inflammation in obese patients to determine which of the two ingredients of Vytorin is responsible for the specific combination of these effects.
- Conditions
- Inflammation, Atherosclerosis, Hypercholesterolemia
- Being tested
- Simvastatin 40mg, Ezetimibe 10mg
- Medical subject headings
- Inflammation, Atherosclerosis, Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 40mgDrug
Also called Simvastatin
Simvastatin administered daily for 6 weeks
Ezetimibe 10mgDrug
Also called Zetia
Ezetimibe administered daily for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin | Active comparator | Obese subjects with elevated cholesterol Receives: Drug: Simvastatin 40mg |
| Ezetimibe | Active comparator | Obese subjects with elevated cholesterol Receives: Drug: Ezetimibe 10mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mRNA Expression of CD68 in MNC
Percentage change in mRNA expression of CD68 in MNC following cream challenge at weeks 0 and 6 of treatment with simvastatin or ezetimibe.
Percent change (using the formula: (x-y)/y*100) is calculated using data collected before (0hr) and after the cream challenge (peak effect) at weeks 0 and 6 of treatment with simvastatin or ezetimibe.
Measured: 6 weeks
Change in mRNA Expression of PECAM on MNC
Percentage change in mRNA expression of PECAM on MNC following cream challenge before and after 6 weeks of treatment with simvastatin or ezetimibe. Percent change (using the formula: (x-y)/y*100) was calculated using data collected before (0hr) and after the cream challenge (peak effect) at weeks 0 and 6 of treatment with simvastatin or ezetimibe.
Measured: 6 weeks
Secondary outcomes (3)
Change in mRNA Expression of IL-1β in MNC
Percentage change in mRNA expression of IL-1β in MNC following cream challenge calculated from data collected before (at 0 week) and after (at 6 weeks) treatment with simvastatin or ezetimibe
Measured: 6 weeks
Change in TNF-a mRNA Expression in MNC
Percentage change in mRNA expression of TNFα in MNC following cream challenge calculated using data collected before and after the cream challenge at weeks 0 and 6 of treatment with simvastatin or ezetimibe
Measured: 6 weeks
Change in mRNA Expression of MMP-9 in MNC
Percentage change in mRNA expression of MMP-9 in MNC calculated from data collected following cream challenge before (0 week) and after (6 weeks) of treatment with simvastatin or ezetimibe
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2020
- Study start1 May 2017
- Primary completion1 Aug 2021
- Study completion1 Nov 2021
Why it stopped: Lack of recruitment- Fellow responsible for study graduated
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 InflammationStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- paresh Dandona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, paresh Dandona, State University of New York at Buffalo
- Investigators
- Paresh Dandona, MD, PhD, Principal investigator, Distinguished Professor of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04638400
- Sponsor's protocol ID
- STUDY00001035
- Status last verified
- Oct 2024
- First submitted
- 7 Oct 2020
- Last updated
- 8 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Effects of Simvastatin Versus Ezetimibe on Intracellular Lipid and Inflammation in Obese Subjects
- ClinicalTrials.gov ID
- NCT04638400
- Acronym / sponsor ID
- STUDY00001035
- Conditions
- Inflammation, Atherosclerosis, Hypercholesterolemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment- Fellow responsible for study graduated
- Enrolment
- 10 participants (actual)
- Lead sponsor
- paresh DandonaUniversity, hospital or other
- Study start
- 1 May 2017 (actual)
- Primary completion
- 1 Aug 2021 (actual)
- Study completion
- 1 Nov 2021 (actual)
- First posted
- 20 Nov 2020 (actual)
- Results
- Posted 23 Jan 2024
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 research study is to determine which of the two ingredients of Vytorin (Simvastatin or Ezetimibe) is responsible for the anti-inflammatory effects of Vytorin
Detailed description
Cardiovascular disease is currently the leading cause of death in the developed countries. Atherosclerosis is the most important cause of cardiovascular disease. Statins are known to exert a powerful anti-atherogenic action which is reflected in a marked beneficial effect on the prevention of cardiovascular effects and cardiovascular mortality. They induce a reduction in the progression and an increase in the regression of atherosclerotic lesions. Statins exert powerful effect on lowering LDLc and are also anti-inflammatory due to their ability to lower CRP concentrations. But little is known about their anti-inflammatory effects at a cellular and molecular levels in humans, in vivo.
Vytorin, a preparation containing simvastatin and ezetimibe, has a powerful effect on lowering LDLc concentration through a combination of effects on the absorption of cholesterol from the gut and hepatic cholesterol biosynthesis. In our previous study we have shown that Vytorin exerts a potent anti-inflammatory effect in the obese in the fasting state and following acute inflammatory changes induced by the intake of cream. The IMPROVE-IT trial, which examined the benefits of adding ezetimibe to simvastatin, showed a small additional benefit of ezetimibe (a 6% reduction in cardiovascular events) compared to simvastatin alone. This is marginal when compared to the established cardiovascular benefits of statins.
We, therefore, explore further into the anti-inflammatory actions of the two components of Vytorin by comparing the effects of simvastatin versus ezetimibe on intracellular lipid and inflammation in obese patients to determine which of the two ingredients of Vytorin is responsible for the specific combination of these effects.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Simvastatin | Active comparator | Drug: Simvastatin 40mgObese subjects with elevated cholesterol |
| Ezetimibe | Active comparator | Drug: Ezetimibe 10mgObese subjects with elevated cholesterol |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age: 18 to 75 years of age.
- Obese (BMI ≥30 kg/m2)
- LDL cholesterol of ≥100 mg/dl
- Not taking any vitamins or antioxidants
Key exclusion criteria (13 listed)
- Currently using anti-hyperlipidemic therapies
- Triglycerides >500 mg/dl.
- Myocardial infarction, angioplasty/stent placement or coronary artery bypass surgery in the past 6 months.
- Patient on chronic use of non-steroidal anti-inflammatory drugs or steroids
- Hepatic disease
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 |
|---|---|---|
| Simvastatin 40mgAlso: SimvastatinSimvastatin administered daily for 6 weeks | Drug | Simvastatin |
| Ezetimibe 10mgAlso: ZetiaEzetimibe administered daily for 6 weeks | Drug | Ezetimibe |
Primary outcome
Change in mRNA Expression of CD68 in MNC
Time frame: 6 weeks
Percentage change in mRNA expression of CD68 in MNC following cream challenge at weeks 0 and 6 of treatment with simvastatin or ezetimibe. Percent change (using the formula: (x-y)/y*100) is calculated using data collected before (0hr) and after the cream challenge (peak effect) at weeks 0 and 6 of treatment with simvastatin or ezetimibe.
Change in mRNA Expression of PECAM on MNC
Time frame: 6 weeks
Percentage change in mRNA expression of PECAM on MNC following cream challenge before and after 6 weeks of treatment with simvastatin or ezetimibe. Percent change (using the formula: (x-y)/y*100) was calculated using data collected before (0hr) and after the cream challenge (peak effect) at weeks 0 and 6 of treatment with simvastatin or ezetimibe.
3 secondary outcomes
Change in mRNA Expression of IL-1β in MNC
Time frame: 6 weeks
Change in TNF-a mRNA Expression in MNC
Time frame: 6 weeks
Change in mRNA Expression of MMP-9 in MNC
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2024.
- 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.
Paresh Dandona, MD, PhD principal investigator
Distinguished Professor of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simvastatin 40mg and Ezetimibe 10mg in people with Inflammation and Atherosclerosis, run by paresh Dandona at 1 site in United States.
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 4 inclusion and 13 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: stopped early, as of the sponsor's last update on 8 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 23 Jan 2024). 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?
Change in mRNA Expression of CD68 in MNC (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 8 Nov 2024.