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

Diabetic Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01796418
• Other study ID #: BESTinDN-001
• Status: Recruiting
• Phase: N/A
• First received: February 19, 2013
• Last updated: December 13, 2013
• Start date: March 2013

Study information

• Verified date: December 2013
• Source: Seoul National University Hospital
• Contact: Chun-Soo Lim, Prof
• Phone: 82-2-870-2120
• Email: cslimjy[@]snu.ac.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

Drug:
• Beraprost sodium

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Kangnam Sacred Heart Hospital	Seoul
Korea, Republic of	Seoul National University Boramae Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Astellas Pharma Korea, Inc.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (12)

Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW, Collins AJ. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol. 2005 Feb;16(2):489-95. Epub 2004 Dec 8. — View Citation

Goya K, Otsuki M, Xu X, Kasayama S. Effects of the prostaglandin I2 analogue, beraprost sodium, on vascular cell adhesion molecule-1 expression in human vascular endothelial cells and circulating vascular cell adhesion molecule-1 level in patients with type 2 diabetes mellitus. Metabolism. 2003 Feb;52(2):192-8. — View Citation

Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54. Erratum in: Ann Intern Med. 2008 Oct 7;149(7):519. — View Citation

Melian EB, Goa KL. Beraprost: a review of its pharmacology and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension. Drugs. 2002;62(1):107-33. Review. — View Citation

Nakayama T, Hironaga T, Ishima H, Maruyama T, Masubuchi Y, Kokubun S. The prostacyclin analogue beraprost sodium prevents development of arterial stiffness in elderly patients with cerebral infarction. Prostaglandins Leukot Essent Fatty Acids. 2004 Jun;70(6):491-4. — View Citation

Nakayama T, Masubuchi Y, Kawauchi K, Masaki R, Hironaga T, Ishima H, Torigoe M, Shimabukuro H. Beneficial effect of beraprost sodium plus telmisartan in the prevention of arterial stiffness development in elderly patients with hypertension and cerebral infarction. Prostaglandins Leukot Essent Fatty Acids. 2007 Jun;76(6):309-14. Epub 2007 Jul 9. — View Citation

Noordzij M, Tripepi G, Dekker FW, Zoccali C, Tanck MW, Jager KJ. Sample size calculations: basic principles and common pitfalls. Nephrol Dial Transplant. 2010 May;25(5):1388-93. doi: 10.1093/ndt/gfp732. Epub 2010 Jan 12. Erratum in: Nephrol Dial Transplant. 2010 Oct;25(10):3461-2. — View Citation

Rubin MF, Rosas SE, Chirinos JA, Townsend RR. Surrogate markers of cardiovascular disease in CKD: what's under the hood? Am J Kidney Dis. 2011 Mar;57(3):488-97. doi: 10.1053/j.ajkd.2010.08.030. Epub 2010 Dec 18. Review. — View Citation

Sato N, Kaneko M, Tamura M, Kurumatani H. The prostacyclin analog beraprost sodium ameliorates characteristics of metabolic syndrome in obese Zucker (fatty) rats. Diabetes. 2010 Apr;59(4):1092-100. doi: 10.2337/db09-1432. Epub 2010 Jan 12. — View Citation

Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007 Jul 3;116(1):85-97. Review. — View Citation

Sugawara A, Kudo M, Saito A, Matsuda K, Uruno A, Ito S. Novel effects of beraprost sodium on vasculatures. Int Angiol. 2010 Apr;29(2 Suppl):28-32. Review. — View Citation

Watanabe M, Nakashima H, Ito K, Miyake K, Saito T. Improvement of dyslipidemia in OLETF rats by the prostaglandin I(2) analog beraprost sodium. Prostaglandins Other Lipid Mediat. 2010 Sep;93(1-2):14-9. doi: 10.1016/j.prostaglandins.2010.04.003. Epub 2010 May 5. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brachial ankle pulse wave velocity (PWV)	The change of brachial ankle PWV at 12 weeks compared to baseline (0 week)	12 weeks	No
Secondary	Ankle brachial indices (ABI)	The change of ABI at 12 weeks compared to baseline (0 week)	12 weeks	No
Secondary	Urine albumin creatinine ratio (UACR)	The change of UACR at 12 weeks compared to baseline (0 week)	12 weeks	No
Secondary	IDMS MDRD estimated glomerular filtration rate (eGFR)	The change of IDMS MDRD eGFR at 12 weeks compared to baseline (0 week)	12 weeks	No
Secondary	Lipid profiles	The change of total cholesterol, LDL-cholesterol, and triglyceride at 12 weeks compared to baseline (0 week)	12 weeks	No
Secondary	Blood pressure	The change of systolic and diastolic blood pressure at 12 weeks compared to baseline (0 week)	12 weeks	No