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

NCT ID: NCT01796418

Last Updated: 2013-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-31

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.

Detailed Description

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Conditions

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Diabetic Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Beraprost sodium

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

Group Type EXPERIMENTAL

Beraprost sodium

Intervention Type DRUG

Placebo

Placebo capsule by mouth every 12 hours for 12 weeks

Group Type PLACEBO_COMPARATOR

No interventions assigned to this group

Interventions

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Beraprost sodium

Intervention Type DRUG

Other Intervention Names

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Berasil

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
Minimum Eligible Age

20 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Korea, Inc.

INDUSTRY

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dong Ki Kim

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Chun-Soo Lim, Prof

Role: STUDY_CHAIR

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

Dong Ki Kim, Prof

Role: PRINCIPAL_INVESTIGATOR

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

Ki Young Na, Prof

Role: PRINCIPAL_INVESTIGATOR

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

Sung Gyun Kim, Prof

Role: PRINCIPAL_INVESTIGATOR

Hallym University Medical Center

Young-Ki Lee, Prof

Role: PRINCIPAL_INVESTIGATOR

Hallym University Kangnam Sacred Heart Hospital

Locations

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Hallym University Sacred Heart Hospital

Anyang, , South Korea

Site Status RECRUITING

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status RECRUITING

Kangnam Sacred Heart Hospital

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Boramae Medical Center

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Chun-Soo Lim, Prof

Role: CONTACT

Phone: 82-2-870-2120

Email: [email protected]

Dong Ki Kim, Prof

Role: CONTACT

Phone: 82-2-2072-2303

Email: [email protected]

Facility Contacts

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Sung Gyun Kim, Prof

Role: primary

Ki Young Na, Prof

Role: primary

Young-Ki Lee, Prof

Role: primary

Chun-Soo Lim, Prof

Role: primary

Dong Ki Kim, Prof

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 17606856 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15590763 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11790158 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20357746 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12601631 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15120711 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17616452 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20450981 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20068136 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21168944 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16908915 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20067907 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24066672 (View on PubMed)

Other Identifiers

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BESTinDN-001

Identifier Type: -

Identifier Source: org_study_id