A Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy

The objectives of this study is:

• To evaluate the efficacy of Probucol on deferring nephropathy development of the patients with diabetic nephropathy (including: the change value of urine albumin from the baseline, the rate of the patients with serum creatinine reaching a doubling of the base-line serum creatinine, the rate of the hemodialysis-free survival).
• To evaluate the efficacy of Cliostazol and Probucol in combination on deferring nephropathy development of the patients with diabetic nephropathy
• To evaluate the efficacy of Cilostazol and Probucol in combination on atherosclerosis related biomarkers change. Atherosclerosis related biomarkers include:(a)Endothelium parameter: ICAM-1, vWF, VCAM-1,and McP-1. (b)Finolysis parameter: TM. (c)Inflammation parameter: Hs-CRP; IL-6. (d)Oxidation parameter: Ox-LDL, 8-OHdG. (e)Lipid parameter: TC, LDL-C, HDL-C, TG.
• To evaluate the efficacy of Cilostazol and Probucol in combination on the progress of carotid intima-media thickness (IMT) on patients with diabetic nephropathy.
• To evaluate the safety of Cilostazol and Probucol in combination on the patients with diabetic nephropathy.

Inclusion criteria

• Male or female age 40~75 years old
• Type 2 diabetes mellitus above 6 months
• HbA1c ≤8%
• Twice (above 2-week interval) confirmed urinary albumin at 30-3000µg/mg.cre
• Receive routine dosage ACEI or ARB treatment above 2 months, and the dosage has been fixed for at least 1 month
• LDL-C>100 mg/dL (2.60 mmol/L) and/ or hyperlipidemia patients with Statins treatment
• Free will to sign the informed consent form

Exclusion criteria

• Has an allergic history to investigational drugs
• Receive antilipemic agents (except Statins) within the latest 2 months, including Probucol
• Receive antiplatelet or anticoagulation agents (except Aspirin) within the latest 2 months, including Cilostazol
• Rapid progression of nephropathy within the latest 3 months
• Kidney disease caused by other reasons according to medical history
• Serum potassium level less than 3.5 mEq/L or more than 5.5 mEq/L
• Hemorrhagic tendency or hemorrhagic disease (such as alimentary tract hemorrhage, active fundus hemorrhage, etc.)
• Has a myocardial infarction, angina pectoris, or cerebral infarction within the latest 3 months
• Congestive heart failure
• Pregnant, potentially pregnant, or lactating woman
• Severe hepatic inadequacy (AST or ALT is 2.5 times higher than the upper limit of the normal value range)
• Serum creatinine level is 1.5 times higher than the upper limit of the normal value range
• Persistent or hardly controlled hypertension (such as malignant hypertension, SBP≥170 mmHg and/ or DBP≥100 mmHg)
• Severe ventricular arrhythmia (such as multiple and multifocal premature ventricular contractions)
• Has a medical history of cardiac syncope or primary syncope
• Has condition that may prolong QT interval (such as congenital long QT syndrome, taking drugs which prolong QT interval, hypokalemia or hypomagnesemia, etc.), or for man QT interval>450msec, for woman QT interval>470msec
• Has severe complication (such as diabetes mellitus ketoacidosis, nonketotic hyperosmolar diabetic coma, malignant tumor, severe anaemia, severe hematologic diseases, etc.)
• Register other clinical trials within the latest 3 months
• Other conditions that would be excluded from this study according to doctors'judgment