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

Study Overview
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Brief Summary
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The efficacy and safety of Cilostazol and Probucol in combination on patients with diabetic nephropathy is better than the single use.

Detailed Description
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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.

Official Title
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A Randomized, Control, Parallel, Open Label, Multi-centre Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy

Conditions
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Diabetic Nephropathy

Intervention / Treatment
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* Drug: Probucol
* Drug: Probucol and Cilostazol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br> | |
| Active Comparator: Probucol<br>Probucol treatment | Drug: Probucol<br>* 250mg,Bid<br>|
| Active Comparator: Combination<br>Probucol and Cilostazol | Drug: Probucol and Cilostazol<br>* 50-100mg,Bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| nephropathy development | After 96-week treatment, compare the efficacy between Probucol group and group control group 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) | 96W | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IMT | After 48-week and 96-week treatment, compare the change value of IMT from the baseline among 3 modality groups. | 48 and 96W | 
| Atherosclerosis related biomarkers | After 12-week, 48-week and 96-week treatment, compare the change value of atherosclerosis related biomarkers from the baseline among 3 modality groups | 48 and 96W | 
| Nephropathy development | 1. After 48-week and 96-week treatment, compare the efficacy among 3 modality groups 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) | 48 and 96W | 
| Adverse events | Incidence of adverse events, clinically relevant abnormal laboratory results before and after treatment (including hemotology, biochemistry, routine urine analysis and glycosylated hemoglobin), abnormal findings of vital sign, physical examination, and 12-lead ECG results | 96W |