Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
2018년 2월 6일 업데이트: Antonio Hernandez Mijares, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients
Coadministration of drugs is common in the pharmacologic treatment of dyslipidemia, with statins and ezetimibe generally constituting the medication of choice.
By acting at different levels, the combination of these drugs allows the therapeutic objective to be achieved.
However, it is not known how these drugs qualitatively affect the composition of lipoprotein subfractions, which differ in size and atherogenic potential.
The investigators set out to evaluate this effect as well as their effects on inflammatory, oxidative stress and endothelial function parameters.
연구 개요
상세 설명
The study consisted of a randomised parallel trial and took place during a period of 2 months.
A total of 42 hyperlipidemic patients were randomly assigned to one of 2 groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
연구 유형
중재적
등록 (실제)
42
단계
- 해당 없음
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- LDL cholesterol concentration of between 160-190 mg/dl in patients with less than 2 cardiovascular risk factors
- LDL concentration of between 130-160 mg/dl in patients that presented 2 or more cardiovascular risk factors.
Cardiovascular risk factors were defined as: age (≥ 45 years in men and ≥55 years in women), a smoking habit, hypertension (≥140/90 mmHg), diabetes mellitus, a high-density lipoprotein (HDL) cholesterol concentration of ≤ 40mg/dl, and a family history of cardiovascular disease.
Exclusion Criteria:
- Triglyceride concentration > 400 mg/dl
- Diabetes Mellitus
- Kidney, liver, or thyroid disease
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Simvastatin
Hyperlipidemic patients received simvastatin (40 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
|
simvastatin (40 mg/day) for 4 weeks
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
|
|
실험적: Ezetimibe
Hyperlipidemic patients received ezetimibe (10 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
|
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
ezetimibe (10 mg/day) for 4 weeks
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Total cholesterol concentration was measured by enzymatic assay
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Baseline, 4 weeks and 8 weeks
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Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
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Baseline, 4 weeks and 8 weeks
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High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
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Baseline, 4 weeks and 8 weeks
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Triglycerides Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Triglyceride concentration were measured by enzymatic assay
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Baseline, 4 weeks and 8 weeks
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Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
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Baseline, 4 weeks and 8 weeks
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Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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LDL subfractions were separated by high-resolution polyacrylamide gel tubes using the Lipoprint® system.
The LDL electrophoretic profile allows 2 patterns to be defined: pattern A or large and buoyant LDL, and pattern non-A or small and dense LDL.
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Baseline, 4 weeks and 8 weeks
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Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Levels of apolipoprotein B were determined by inmunonephelometry
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Baseline, 4 weeks and 8 weeks
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
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Baseline, 4 weeks and 8 weeks
|
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Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
|
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Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
|
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Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
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Baseline, 4 weeks and 8 weeks
|
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Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
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Baseline, 4 weeks and 8 weeks
|
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Membrane Potential Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
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Baseline, 4 weeks and 8 weeks
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Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
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Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
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Baseline, 4 weeks and 8 weeks
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Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.
Leukocyte rolling was estimated as the number of leukocytes rolling over 100 μm2 of the endothelial monolayer during a 1-min period.
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Baseline, 4 weeks and 8 weeks
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Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.
Adhesion was evaluated by counting the number of polymorphonuclear cells that maintained stable contact with human umbilical vein endothelial cells (HUVEC) for 30 seconds.
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Baseline, 4 weeks and 8 weeks
|
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Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.The rolling velocity in the field of focus was determined by measuring the time required by 20 consecutive leukocytes to cover a distance of 100 μm.
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Baseline, 4 weeks and 8 weeks
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Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
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Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
|
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Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
기간: Baseline, 4 weeks and 8 weeks
|
E-selectin was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Antonio Hernández, MD, Phd, FISABIO - University Hospital Dr Peset
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Berneis K, Rizzo M, Berthold HK, Spinas GA, Krone W, Gouni-Berthold I. Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial. Eur Heart J. 2010 Jul;31(13):1633-9. doi: 10.1093/eurheartj/ehq181. Epub 2010 Jun 6.
- Florentin M, Liberopoulos EN, Moutzouri E, Rizos CV, Tselepis AD, Elisaf MS. The effect of simvastatin alone versus simvastatin plus ezetimibe on the concentration of small dense low-density lipoprotein cholesterol in subjects with primary hypercholesterolemia. Curr Med Res Opin. 2011 Mar;27(3):685-92. doi: 10.1185/03007995.2010.546394. Epub 2011 Jan 27.
- Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, Johnson-Levonas AO, Sapre A, Donahue SR; Ezetimibe Study Group. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004 Nov;26(11):1758-73. doi: 10.1016/j.clinthera.2004.11.016.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2009년 1월 1일
기본 완료 (실제)
2011년 12월 1일
연구 완료 (실제)
2011년 12월 1일
연구 등록 날짜
최초 제출
2014년 11월 25일
QC 기준을 충족하는 최초 제출
2014년 11월 26일
처음 게시됨 (추정)
2014년 12월 2일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2018년 3월 8일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 2월 6일
마지막으로 확인됨
2018년 2월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
Simvastatin에 대한 임상 시험
-
Enrique de-MadariaFundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana 그리고 다른 협력자들종료됨