Effect of Diabetes Mellitus on Cholesterol Absorption, Synthesis and Statin Efficacy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Changes in LDL Cholesterol
研究概览
简要总结
HMG CoA reductase inhibitors (statins) are commonly used to treat high cholesterol (HC) in both type 1 and type 2 diabetes mellitus (DM). Several studies have shown benefits of statin among patients of type 2 DM, however, no such data is available for patients with type 1 DM.
It is known from studies on cholesterol metabolism using surrogate markers that patients with type 1 DM have higher cholesterol absorption compared to normals and those with type 2 DM have higher cholesterol synthesis. Since statins inhibit synthesis, patients with type 1 DM may not have a good response and may respond better to cholesterol absorption inhibitors. The purpose of this study is to determine the cholesterol lowering effects of cholesterol absorption inhibitors and cholesterol synthesis inhibitors in subjects with type 1 and type 2 diabetes mellitus.
详细描述
Hypothesis:
- Cholesterol absorption inhibitors like ezetimibe are more effective in lowering cholesterol in subjects with type 1 diabetes mellitus . The primary outcome measures are LDL cholesterol and cholesterol tracer absorption.
- Cholesterol synthesis inhibitors like statins are more effective in lowering cholesterol in subjects with type 2 diabetes mellitus. The primary outcomes are LDL cholesterol and 24 Hour urinary mevalonic acid levels.
- Response to statin is related to basal cholesterol synthesis rates. The primary outcomes are LDL cholesterol and 24 Hour urinary mevalonic acid levels.
- Response to ezetimibe is related to basal absorption rates. The primary outcome measures are LDL cholesterol, phytosterol levels and cholesterol tracer absorption.
Specific Aims:
- Measure baseline sterol absorption using plant sterol levels and and synthesis by using 24 h excretion of urinary mevalonic acid levels in type 1 and type 2 subjects
- Measure changes in lipid parameters, cholesterol synthesis and absorption markers in type 1 and type 2 subjects before and after 6 week therapy with simvastatin and 6 week therapy with ezetimibe after a 4 week washout period
- Start collecting blood for future genetic analysis for polymorphisms in cholesterol absorption genes
Specific Methods:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 DM:
- •Age > 18 years
- •Subjects diagnosed with type 1 DM (diagnosed based upon history of ketoacidosis, proven insulin dependence, absent C-peptide and or positive autoantibody profile (such as anti-GAD etc.)
- •Stable A1C < 8.5%
- •BMI < 31
- •Type 2 DM:
- •Age > 18 years
- •Subjects diagnosed with type II DM (diagnosed as adult onset, not-insulin dependent and not on insulin)
- •Stable A1C < 8.5%
- •BMI < 31
排除标准
- •History of active, unstable cardiovascular disease (including MI, CHF, Stroke, Angina, CABG, stenting/PTCA, peripheral vascular disease, intermittent claudication)
- •Pregnancy, nursing or likely to get pregnant during the course of the study (not on oral contraceptives and premenopausal)
- •Chronic Kidney Disease (creatinine > 2.0)
- •Liver function test abnormalities, not previously worked up (AST or ALT >4x upper limit of normal)
- •Active substance abuse including alcohol
- •History of severe Hypertriglyceridemia (untreated TG > 500) and on therapy
- •Use of agents that interfere with cholesterol absorption (such as fiber, resins etc.) which can not be discontinued for the duration of the study
- •Actively enrolled in a weight loss program or following a special diet ( e.g.: Atkins diet)
- •History of malignancy <5y
- •History of Rhabdomyolysis and Myopathy
- •Use of on-going oral corticosteroids
- •History of HIV infection
- •Use of following drugs/compounds: cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, niacin, amiodarone, verapamil or large quantities of grape fruit juice (> 1 quart per day)
- •Proteinuria: more than or equal to 300mg/24 hours calculated from random urine specimen.
- •Anyone with hypersensitivity to either one of the study medications
- •Allergy to Soy bean products
- •Unable to consume milk products with or without Lactaid®
研究组 & 干预措施
Subjects with type 1 diabetes mellitus, option 1
Half the subjects will start with arm (i.e. every other subject in order)
- Simvastatin 40 mg tablet by month daily for 6 weeks,
- 4 weeks washout period
Half the subjects will start with arm (i.e. every other subject in order)
- Ezetimibe 10 mg by month for 6 weeks
- 4 weeks washout period
- Simvastatin 40 mg tablet by month daily for 6 weeks
干预措施: simvastatin or ezetimibe (Drug)
Subjects with type 2 diabetes mellitus option 1
Half the subjects will start with arm (i.e. every other subject in order)
- Simvastatin 40 mg tablet by month daily for 6 weeks,
- 4 weeks washout period
Half the subjects will start with arm (i.e. every other subject in order)
- Ezetimibe 10 mg by month for 6 weeks
- 4 weeks washout period
- Simvastatin 40 mg tablet by month daily for 6 weeks
干预措施: simvastatin or ezetimibe (Drug)
Subjects with type 1 diabetes mellitus, option 2
Half the subjects will start with arm (i.e. every other subject in order)
- Ezetimibe 10 mg by month for 6 weeks,
- 4 weeks washout period
干预措施: simvastatin or ezetimibe (Drug)
Subjects with type 2 diabetes mellitus option 2
Half the subjects will start with arm (i.e. every other subject in order) Ezetimibe 10 mg by month for 6 weeks,
•4 weeks washout period
干预措施: simvastatin or ezetimibe (Drug)
结局指标
主要结局
Changes in LDL Cholesterol
时间窗: 6 weeks after starting drug therapy
Subjects with T1DM or T2DM were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design. The data are reported as follows. Subjects with type 1 diabetes mellitus: Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order) Subjects with type 2 diabetes mellitus: Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order)
次要结局
- Changes in Cholesterol Absorption or Synthesis Rates From the Baseline(6 weeks after initiation of drug therapy)
研究者
Srividya Kidambi, MD
Assistant Professor, Endocrinology
Medical College of Wisconsin