Platelet Function in Diabetic Patients With and Without Renal Impairment, and the Effects of Lipid Lowering Treatment

Study Overview
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Brief Summary
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The purpose of this study is compare the effects of simvastatin+ezetimibe with those of simvastatin alone on platelet activity, platelet-leukocyte interactions and inflammatory variables in diabetic patients with or without impaired renal function.

Detailed Description
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A detailed study protocol is available.

Official Title
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Platelet Function in Diabetic Patients With and Without Renal Impairment, and the Effects of Lipid Lowering Treatment

Conditions
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Diabetes Mellitus, Impaired Renal Function

Intervention / Treatment
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* Drug: Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes mellitus type 1 or type 2 With or without established microalbuminuria (albumin-to-creatinine ratio (ACR)2,5-25 mg/mmol for men, and 3,5-25 mg/mmol for women, according to ISH and ESC recommended criteria) Glomerular filtration rate (GFR) between 15-60 ml/min/1.73m2 (measured the last 6 months) or GFR >75ml/min/1.73m2. The abbreviated Modification of Diet in Renal Disease (MDRD) equation will be used to calculate GFR. Age 18-80 years Exclusion Criteria: Definite history of myocardial infarction, coronary revascularisation procedure or stroke. (i.e, a strong clinical indication for statin treatment) Functioning renal transplant, or living donor-related transplant planned. Patients on dialysis. Poor metabolic control, i.e HbA1c > 9% Definite history of chronic liver disease, or abnormal liver function (i.e ALT >1,5 x ULN or, if ALT not available, AST > 1,5 x ULN). Evidence of active inflammatory muscle disease (e.g dermatomyositis, polymyositis), or CK>3 x ULN; Definite previous adverse reaction to a statin or to ezetimibe Definite previous adverse reaction to acetylsalicylic acid. Definite previous adverse reaction to an ACE-inhibitor. Need for concomitant treatment with a strong inhibitor of CYP3A4, such as itrokonazole, ketokonazole, erythromycin, clarithromycin, HIV-protease inhibitors or nefazodone (i.e. agents that may markedly elevate simvastatin levels).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: simvastatin + ezetimibe<br>Cross-over study with placebo only run-in period. All patients participate in this arm with simvastatin + ezetimibe either as first treatment period (8-10 weeks)or second treatment period (8-10 weeks). The primary comparison is ezetimibe vs. placebo on top of simvastatin. A secondary comparison will be simvastatin vs. placebo run-in. | Drug: Ezetimibe<br>* After a placebo only run-in period patients (two groups) are treated with simvastatin + ezetimibe and simvastatin + placebo in a cross-over trial. Ezetimibe effects on top of simvastatin will be evaluated as the primary aim; simvastatin effects compared to run-in on placebo will be evaluated as a secondary aim.<br>* Other names: Ezetrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effects of simvastatin + ezetimibe with those of simvastatin alone, on thrombogenic mechanisms, in patients with diabetes mellitus type 2. |  | 6 weeks, 14-18 weeks, 22-24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare effects of simvastatin alone with those of placebo on thrombogenic mechanisms. Compare the effects of simvast. + ezetim. with those of simvast. alone on inflammatory variables. Assess how the treatment effect relate to renal function. |  | 6 weeks, 14-18 weeks, 22-24 weeks |