InflammationNCT01420328
To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects
A study testing Vytorin in people with Inflammation, run by University at Buffalo at 1 site in United States.
Trial summary
This study focuses on the use of Vytorin to study inflammatory markers in subjects with normal cholesterol. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammation
- What is being tested?
- Vytorin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2011to 1 Jul 2016
- Phase
- Interventional
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-65years.
- Obese BMI >30kg/m2
- LDL cholesterol >100 mg/dl
- Written and informed consent signed and dated 5. Not on any vitamin/antioxidants
Who cannot join
- On any antilipid agents.
- Triglyceride >500mg/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 12Show 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 13. Anemia with hemoglobin <12 g/dl
Trial locations and contacts
1 site in 1 country.
United States1 site
Diabetes Endocrinology Center of WNY
Buffalo, New York, 14209
About this study
This study focuses on the use of Vytorin to study inflammatory markers in subjects with normal cholesterol.
Read the detailed description
Following the first demonstration by our group that macronutrient (glucose, cream and a high fat high carbohydrate meal) intake results in increased ROS generation and oxidative stress at the cellular and molecular level, the investigators have now shown in our preliminary data that cream intake induces comprehensive inflammation as reflected in increased intranuclear NFkB binding, decreased IkBα expression, increased expression of IL-1β, IL-12, TNFα and other pro-inflammatory mediators. While carrying out these experiments, the investigators asked whether cream intake was associated with an uptake of lipid by peripheral blood mononuclear cells (MNC). Indeed, there was a significant increase in intracellular lipid which was visualized as intracellular lipid droplets. The increase in intracellular lipid droplets was associated with an increase in intracellular superoxide generation; the expression of CD68, a marker for macrophages; and PECAM, the adhesion molecule which mediates trans- endothelial transfer of leucocytes. The investigators also found that the lipid fractions to increase were cholesterol ester, triglyceride and fatty acids. In view of the tantalizing observation that the lipid droplet laden MNC appeared to be monocytes, looked like foam cells and the fact that CD68 expression had increased, there is a possibility that foam cells may be formed in peripheral circulation by monocytes after a lipid rich meal. This simple model of foam cell formation also lends itself for the study of the effect of various lipid lowering drugs. Our investigation will be the first to study this novel paradigm. The investigators plan to study the effect of a cholesterol lowering agent, Vytorin (simvastatin and ezetimibe), on intracellular lipid in MNC, expression of CD68 and PECAM, ROS generation and inflammation in obese subjects. This investigation may provide an additional mechanism of action by which these drugs may reduce atherosclerosis.
- Conditions
- Inflammation
- Being tested
- Vytorin, Placebo
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VytorinDrug
Also called Ezetimibi/Simvastatin 10/40
Simvastatin 40 mg and Ezetimibe 10 mg daily combination pill (Vytorin) for 6 weeks
PlaceboDrug
Also called Placebo for Vytorin
Placebo treatment for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo Arm | Placebo comparator | Obese subjects treated with placebo for 6 weeks Receives: Drug: Placebo |
| Vytorin Arm | Active comparator | Obese subjects treated with Vytorin for 6 weeks Receives: Drug: Vytorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in CD68 mRNA Expression in MNC
Percent change from baseline (0 week) in cream challenge induced change in CD68 mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo.
Outcome calculated as: (change at 6 weeks- change at 0 week)/ change at 0 week*100
Measured: 0 weeks and 6 weeks
Secondary outcomes (3)
Change in Cream-induced Expression of CD16
Percent change from baseline (0 week) in cream -induced change in CD16 mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo.
Outcome calculated as: (change at 6 weeks- change at 0 week)/ change at 0 week*100
Measured: 6 weeks
Change IL-1b mRNA Expression
Percent change from baseline (0 week) in cream -induced change in IL-1b mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo.
Outcome calculated as: (change at 6 weeks- change at 0 week)/ change at 0 week*100
Measured: 6 weeks
Change in Plasma Endotoxin (LPS) Concentrations
change from baseline (0 week) in cream -induced change in plasma endotoxin concentration after 6 weeks of treatment with Vytorin or placebo.
Outcome calculated as: (change at 6 weeks- change at 0 week)
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 posted19 Aug 2011 (estimated)
- Study start1 May 2011
- Primary completion1 Jul 2015
- Study completion1 Jul 2016
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 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University at Buffalo
- Sponsor type
- University, hospital or other
- Collaborators
- Kaleida Health
- Responsible party
- Principal investigator, Paresh Dandona, University at Buffalo
- Investigators
- Paresh Dandona, MD, Principal investigator, University at Buffalo, NY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01420328
- Sponsor's protocol ID
- MED7120311A
- Status last verified
- Mar 2024
- First submitted
- 26 May 2011
- Last updated
- 17 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ghanim H, Green K, Abuaysheh S, Patel R, Batra M, Chaudhuri A, Makdissi A, Kuhadiya ND, Dandona P. Ezetimibe and simvastatin combination inhibits and reverses the pro-inflammatory and pro-atherogenic effects of cream in obese patients. Atherosclerosis. 2017 Aug;263:278-286. doi: 10.1016/j.atherosclerosis.2017.06.010. Epub 2017 Jun 7.
PubMed 28711708
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects
- ClinicalTrials.gov ID
- NCT01420328
- Acronym / sponsor ID
- MED7120311A
- Conditions
- Inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University at BuffaloUniversity, hospital or other
- Collaborators
- Kaleida Health
- Study start
- 1 May 2011 (actual)
- Primary completion
- 1 Jul 2015 (actual)
- Study completion
- 1 Jul 2016 (actual)
- First posted
- 19 Aug 2011 (estimated)
- Results
- Posted 17 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study focuses on the use of Vytorin to study inflammatory markers in subjects with normal cholesterol.
Detailed description
Following the first demonstration by our group that macronutrient (glucose, cream and a high fat high carbohydrate meal) intake results in increased ROS generation and oxidative stress at the cellular and molecular level, the investigators have now shown in our preliminary data that cream intake induces comprehensive inflammation as reflected in increased intranuclear NFkB binding, decreased IkBα expression, increased expression of IL-1β, IL-12, TNFα and other pro-inflammatory mediators. While carrying out these experiments, the investigators asked whether cream intake was associated with an uptake of lipid by peripheral blood mononuclear cells (MNC). Indeed, there was a significant increase in intracellular lipid which was visualized as intracellular lipid droplets. The increase in intracellular lipid droplets was associated with an increase in intracellular superoxide generation; the expression of CD68, a marker for macrophages; and PECAM, the adhesion molecule which mediates trans- endothelial transfer of leucocytes. The investigators also found that the lipid fractions to increase were cholesterol ester, triglyceride and fatty acids. In view of the tantalizing observation that the lipid droplet laden MNC appeared to be monocytes, looked like foam cells and the fact that CD68 expression had increased, there is a possibility that foam cells may be formed in peripheral circulation by monocytes after a lipid rich meal. This simple model of foam cell formation also lends itself for the study of the effect of various lipid lowering drugs. Our investigation will be the first to study this novel paradigm. The investigators plan to study the effect of a cholesterol lowering agent, Vytorin (simvastatin and ezetimibe), on intracellular lipid in MNC, expression of CD68 and PECAM, ROS generation and inflammation in obese subjects. This investigation may provide an additional mechanism of action by which these drugs may reduce atherosclerosis.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo Arm | Placebo comparator | Drug: PlaceboObese subjects treated with placebo for 6 weeks |
| Vytorin Arm | Active comparator | Drug: VytorinObese subjects treated with Vytorin for 6 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-65years.
- Obese BMI >30kg/m2
- LDL cholesterol >100 mg/dl
- Written and informed consent signed and dated 5. Not on any vitamin/antioxidants
Key exclusion criteria (12 listed)
- On any antilipid agents.
- Triglyceride >500mg/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 |
|---|---|---|
| VytorinAlso: Ezetimibi/Simvastatin 10/40Simvastatin 40 mg and Ezetimibe 10 mg daily combination pill (Vytorin) for 6 weeks | Drug | Vytorin Arm |
| PlaceboAlso: Placebo for VytorinPlacebo treatment for 6 weeks | Drug | Placebo Arm |
Primary outcome
Change in CD68 mRNA Expression in MNC
Time frame: 0 weeks and 6 weeks
Percent change from baseline (0 week) in cream challenge induced change in CD68 mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo. Outcome calculated as: (change at 6 weeks- change at 0 week)/ change at 0 week*100
3 secondary outcomes
Change in Cream-induced Expression of CD16
Time frame: 6 weeks
Change IL-1b mRNA Expression
Time frame: 6 weeks
Change in Plasma Endotoxin (LPS) Concentrations
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 17 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28711708Ghanim H, Green K, Abuaysheh S, Patel R, Batra M, Chaudhuri A, Makdissi A, Kuhadiya ND, Dandona P. Ezetimibe and simvastatin combination inhibits and reverses the pro-inflammatory and pro-atherogenic effects of cream in obese patients. Atherosclerosis. 2017 Aug;263:278-286. doi: 10.1016/j.atherosclerosis.2017.06.010. Epub 2017 Jun 7.
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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 principal investigator
University at Buffalo, NY
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vytorin in people with Inflammation, run by University at Buffalo 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 12 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 17 Apr 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 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 CD68 mRNA Expression in MNC (time frame: 0 weeks and 6 weeks). 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 NCT01420328, 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 17 Apr 2024.