Beraprost Sodium and Arterial Stiffness in Patients With Type 2 Diabetic Nephropathy

Study Overview
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Brief Summary
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Diabetic nephropathy, the leading cause of end-stage renal disease in many countries, is characterized by high cardiovascular mortality and morbidity even in the early course of the disease. In addition, cardiovascular complication has been the most common cause of death in these patients. Thus, early detection and appropriate intervention for this highly common and critical complication is considered to play an important role in the management of the disease. In this regard, much interest has been focused on the early markers which can predict arterial diseases before the clinically apparent cardiovascular diseases. Recently, glowing evidence suggests that arterial stiffness as assessed by pulse wave velocity (PWV) may serve as a surrogate marker for future cardiovascular disease. In fact, increased PWV has been known to be independently associated with diabetic nephropathy in type 2 diabetes. Beraprost sodium (BPS) is a stable orally active prostacyclin (PGI2) analogue that has a potent vasodilatory and anti-platelet effect. Also, BPS has been suggested to improve a micro-vascular circulation through a reduction of red blood cell deformability. In addition, recent studies have demonstrated that BPS improves endothelial function through an increase in endothelial nitric oxide synthesis and NO synthase gene transcription. These beneficial effects of BPS have been known to reduce PWV in patients prone to cardiovascular diseases such as elderly, hypertension, or a history of cerebral infarction. However, the effect of BPS on arterial stiffness in patients with diabetic nephropathy remains elusive. Our study will address the effect of BPS on arterial stiffness by PWV in patients with diabetic nephropathy.

Official Title
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Effect of Beraprost Sodium on Arterial Stiffness in Patients With Type 2 Diabetic Nephropathy (BESTinDN Study)

Conditions
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Diabetic Nephropathy

Intervention / Treatment
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* Drug: Beraprost sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 19 years or more and 75 years or less Type 2 diabetes who is prescribed glucose-lowering agent or insulin Estimated glomerular filtration rate (GFR) by isotope dilution mass spectrometry (IDMS)- Modification of Diet in Renal Disease (MDRD) equation 30 ml/min/1.73 m2 or more verified 2 times or more of albuminuria 30 mg/g cr (or protein 300 mg/g cr)or more in a spot urine sample with interval of 1 week or more in recent 6 months Patients whose blood pressure is 140/90 mmHg or less and did not receive a prescription for additional antihypertensive medication in recent 3 months Patients who give written consent to this study by oneself Exclusion Criteria: History of kidney transplantation current advanced congestive heart failure (NYHA class III or more) current uncontrolled arrhythmia current advanced liver cirrhosis (Child-Pugh class C) History of bleeding diathesis current active infection or uncontrolled inflammatory disorders History of cerebrovascular accident or myocardial infarction current use of anticoagulant current use of two or more antiplatelet agents patients with advanced malignancy (life expectancy less than 6 months) patients with uncontrolled diabetes (Hba1c more than 10%) patients with severe anemia (Hb less than 8.0 g/dL) female who are pregnant, trying to get pregnant or lactating Genetic diseases such as galactose intolerance, lactose deficiency or glucose-galactose malabsorption

Ages Eligible for Study
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Minimum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beraprost sodium<br>Beraprost sodium 0.02 mg capsule by mouth every 12 hours for 12 weeks | Drug: Beraprost sodium<br> <br> * Other names: Berasil;|
| Placebo Comparator: Placebo<br>Placebo capsule by mouth every 12 hours for 12 weeks | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial ankle pulse wave velocity (PWV) | The change of brachial ankle PWV at 12 weeks compared to baseline (0 week) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankle brachial indices (ABI) | The change of ABI at 12 weeks compared to baseline (0 week) | 12 weeks | 
| Urine albumin creatinine ratio (UACR) | The change of UACR at 12 weeks compared to baseline (0 week) | 12 weeks | 
| IDMS MDRD estimated glomerular filtration rate (eGFR) | The change of IDMS MDRD eGFR at 12 weeks compared to baseline (0 week) | 12 weeks | 
| Lipid profiles | The change of total cholesterol, LDL-cholesterol, and triglyceride at 12 weeks compared to baseline (0 week) | 12 weeks | 
| Blood pressure | The change of systolic and diastolic blood pressure at 12 weeks compared to baseline (0 week) | 12 weeks |