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

NCT01796418 | Unknown

• 1 other identifier: BESTinDN-001
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Diabetic Nephropathy

Outcome Measures

Primary Outcomes (1)

• Brachial ankle pulse wave velocity (PWV)

  The change of brachial ankle PWV at 12 weeks compared to baseline (0 week)

  12 weeks

Secondary Outcomes (5)

• Ankle brachial indices (ABI)

  12 weeks

• Urine albumin creatinine ratio (UACR)

  12 weeks

• IDMS MDRD estimated glomerular filtration rate (eGFR)

  12 weeks

• Lipid profiles

  12 weeks

• Blood pressure

  12 weeks

Study Arms (2)

Beraprost sodium

EXPERIMENTAL

Beraprost sodium 0.02 mg capsule by mouth every 12 hours for 12 weeks

Drug: Beraprost sodium

Placebo

PLACEBO COMPARATOR

Placebo capsule by mouth every 12 hours for 12 weeks

Interventions

Beraprost sodium DRUG

Also known as: Berasil

Beraprost sodium

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Astellas Pharma Korea, Inc.: collaborator

Study Sites (5)

Hallym University Sacred Heart Hospital

Anyang, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, South Korea

RECRUITING

Kangnam Sacred Heart Hospital

Seoul, South Korea

RECRUITING

Seoul National University Boramae Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Related Publications (13)

• Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007 Jul 3;116(1):85-97. doi: 10.1161/CIRCULATIONAHA.106.678342.

  PMID: 17606856 BACKGROUND

• 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. doi: 10.1681/ASN.2004030203. Epub 2004 Dec 8.

  PMID: 15590763 BACKGROUND

• 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. doi: 10.2165/00003495-200262010-00005.

  PMID: 11790158 BACKGROUND

• 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.

  PMID: 20357746 BACKGROUND

• 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. doi: 10.1053/meta.2003.50025.

  PMID: 12601631 BACKGROUND

• 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. doi: 10.1016/j.plefa.2003.10.004.

  PMID: 15120711 BACKGROUND

• 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. doi: 10.1016/j.plefa.2007.05.004. Epub 2007 Jul 9.

  PMID: 17616452 BACKGROUND

• 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.

  PMID: 20450981 BACKGROUND

• 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.

  PMID: 20068136 BACKGROUND

• 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.

  PMID: 21168944 BACKGROUND

• 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. doi: 10.7326/0003-4819-145-4-200608150-00004.

  PMID: 16908915 BACKGROUND

• 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.

  PMID: 20067907 BACKGROUND

• Na KY, Kim DK, Kim SG, Lee YK, Lim CS. Effect of beraprost sodium on arterial stiffness in patients with type 2 diabetic nephropathy. Trials. 2013 Sep 2;14:275. doi: 10.1186/1745-6215-14-275.

  PMID: 24066672 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

beraprost

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Chun-Soo Lim, Prof

  Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea

  STUDY CHAIR

• Dong Ki Kim, Prof

  Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

  PRINCIPAL INVESTIGATOR

• Ki Young Na, Prof

  Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

  PRINCIPAL INVESTIGATOR

• Sung Gyun Kim, Prof

  Hallym University Medical Center

  PRINCIPAL INVESTIGATOR

• Young-Ki Lee, Prof

  Hallym University Kangnam Sacred Heart Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chun-Soo Lim, Prof

CONTACT

82-2-870-2120; cslimjy@snu.ac.kr

Dong Ki Kim, Prof

CONTACT

82-2-2072-2303; dkkim73@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 19, 2013
• First Posted: February 21, 2013
• Study Start: March 1, 2013
• Primary Completion: August 1, 2014
• Last Updated: December 16, 2013

Record last verified: 2013-12

Locations

KR (5)