Effect of Sulodexide on Albuminuria in Chinese Type 2 Diabetic Patients (Soften)

• ClinicalTrials.gov Identifier: NCT01316068
• Recruitment Status: Unknown
• First Posted: March 16, 2011
• Last Update Posted: March 16, 2011
• Sponsor: Sun Yat-sen University
• Collaborator: ALFA WASSERMANN（BJ) Market Research and Management Co., Ltd
• Information provided by: Sun Yat-sen University

Study Description

Brief Summary:

Current therapies targeting albuminuria in diabetic nephropathy leave residual urinary albumin secretion, which meanwhile leave residual cardiovascular risk. Previous studies demonstrated that sulodexide could reduce albuminuria in type 2 diabetic patients. But no data concerning Chinese population is available. The investigators aim to provide evidence of effects of sulodexide on diabetic nephropathy in Chinese diabetic patients. Further the investigators also test the hypothesis that sequential administration of intravenous and oral replacement of the drug would gain an earlier and greater reduction of albuminuria, compared with oral use only.

Condition or disease	Intervention/treatment	Phase
Diabetic Nephropathy; Albuminuria	Drug: intravenous use of sulodexide followed by oral use; Drug: use of sulodexide orally only	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Intravenous and Oral Therapy With Sulodexide on Albuminuria in Type 2 Diabetic Patients
• Study Start Date: March 2011
• Estimated Primary Completion Date: August 2012
• Estimated Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: sequencial use of sulodexide; Patients will be given sulodexide 1200 LSU per day intravenously for 2 weeks. Then patients will receive 1000 LSU per day orally for 50 weeks.	Drug: intravenous use of sulodexide followed by oral use; Patients will be given sulodexide 1200 LSU per day intravenously for 2 weeks,then receive 1000 LSU per day orally for 50 weeks.; Other Name: sequential use of sulodexide
Active Comparator: oral use of sulodexide; Patients allocated to oral group will received 1000 LSU per day orally for 52 weeks	Drug: use of sulodexide orally only; Patients receive 1000 LSU per day orally for 52 weeks; Other Name: oral use of sulodexide

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in urine albumin/creatinine ratio [ Time Frame: 52th week since the commence of therapy ]
   conversion to normoalbuminuria and at least a 25% reduction in UACR opposed to baseline, or 50% reduction in UACR opposed to baseline

Secondary Outcome Measures :

1. Change from Baseline in urine albumin/creatinine ratio and serum creatinine [ Time Frame: before and 2nd,12th,24th,36th and 60th week since the commence of therapy ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of type 2 diabetes based on WHO criteria
• Age 18-75 years old
• Serum creatinine ≤ 1.5 mg/dL (130umol/L)
• Albuminuria defined by a urine albumin/creatinine ratio(ACR) according to ADA criteria 2009 (microalbuminuria by 30-299 ug albumin/mg creatinine and macroalbuminuria by ≥300 ug albumin/mg creatinine on random spot urine collection )
• Continued stable seated systolic blood pressure < 180 mmHg and diastolic blood pressure < 110 mmHg
• Willing to change antihypertensive medication regimen if necessary
• Willing to provide written informed consent to participate in the study
• Willing to take contraception,or infertility for the duration of the study

Exclusion Criteria:

• Type 1 diabetes mellitus
• Present acute diabetic complication, or severe chronic diabetic complication(e.g. proliferative diabetic retinopathy)
• Complicating uncontrolled severe infection
• Hepatic insufficiency or renal insufficiency or severe disturbance of lipid metabolism
• Blood pressure ≥ 180/110mmHg
• Severe concomitant systemic disease(e.g. cardiac insufficiency, stroke), anticipated to be unable to finish the trial
• Uncooperative,unable to follow up, or anticipated unable to finish the trial
• Patients with other known specific renal diseases
• Untreated urinary tract infection that would impact urinary protein values
• Evidence of hepatic dysfunction including total bilirubin > 2.0 mg/dL (34 mmol/L) or elevated transaminases
• History of Cardiovascular disease as follows: Unstable angina pectoris, myocardial infarction, transient ischemic attack, cerebrovascular accident, New York Heart Association Functional Class III or IV heart failure, obstructive valvular heart disease or hypertrophic cardiomyopathy
• Any risk of bleeding, or platelet count < 100×109/L or anticipated surgery within research period
• Active, recurrent or metastatic cancer, or known HIV infection
• Participant in any experimental drug study in the past 90 days prior to the enrollment of the study, or plan to participate in any drug study during the study period
• Prior exposure to sulodexide, either in a clinical setting or as a participant in another clinical study
• Known allergy or intolerance to any heparin-like compounds or multiple drug allergies
• Lactation, pregnancy, or an anticipated or planned pregnancy during the study period
• Inability to give an informed consent or to cooperate with researchers (e.g. psychiatric disorder) or history of noncompliance to medical regimen

Contacts and Locations

Locations

China, Guangdong

endocrinology department of the first affiliated hospital of Sun Yat-sen University

Guangzhou, Guangdong, China, 510080

Sponsors and Collaborators

Sun Yat-sen University

ALFA WASSERMANN（BJ) Market Research and Management Co., Ltd

Investigators

• Principal Investigator: Yanbing Li, PhD; First Affiliated Hospital, Sun Yat-Sen University

More Information

Publications:

Blouza S, Dakhli S, Abid H, Aissaoui M, Ardhaoui I, Ben Abdallah N, Ben Brahim S, Ben Ghorbel I, Ben Salem N, Beji S, Chamakhi S, Derbel A, Derouiche F, Djait F, Doghri T, Fourti Y, Gharbi F, Jellouli K, Jellazi N, Kamoun K, Khedher A, Letaief A, Limam R, Mekaouer A, Miledi R, Nagati K, Naouar M, Sellem S, Tarzi H, Turki S, Zidi B, Achour A; DAVET (Diabetic Albuminuria Vessel Tunisia Study Investigators). Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2010 Jul-Aug;23(4):415-24.

Chen S, Fang Z, Zhu Z, Deng A, Liu J, Zhang C. Protective effect of sulodexide on podocyte injury in adriamycin nephropathy rats. J Huazhong Univ Sci Technolog Med Sci. 2009 Dec;29(6):715-9. doi: 10.1007/s11596-009-0608-0. Epub 2009 Dec 29.

Rossini M, Naito T, Yang H, Freeman M, Donnert E, Ma LJ, Dunn SR, Sharma K, Fogo AB. Sulodexide ameliorates early but not late kidney disease in models of radiation nephropathy and diabetic nephropathy. Nephrol Dial Transplant. 2010 Jun;25(6):1803-10. doi: 10.1093/ndt/gfp724. Epub 2010 Jan 7.

Lewis EJ, Xu X. Abnormal glomerular permeability characteristics in diabetic nephropathy: implications for the therapeutic use of low-molecular weight heparin. Diabetes Care. 2008 Feb;31 Suppl 2:S202-7. doi: 10.2337/dc08-s251.

Weiss R, Niecestro R, Raz I. The role of sulodexide in the treatment of diabetic nephropathy. Drugs. 2007;67(18):2681-96. doi: 10.2165/00003495-200767180-00004.

Sulikowska B, Olejniczak H, Muszynska M, Odrowaz-Sypniewska G, Gaddi A, Savini C, Cicero AF, Laghi L, Manitius J. Effect of sulodexide on albuminuria, NAG excretion and glomerular filtration response to dopamine in diabetic patients. Am J Nephrol. 2006;26(6):621-8. doi: 10.1159/000098195. Epub 2006 Dec 21.

Achour A, Kacem M, Dibej K, Skhiri H, Bouraoui S, El May M. One year course of oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2005 Sep-Oct;18(5):568-74.

Gambaro G, Kinalska I, Oksa A, Pont'uch P, Hertlova M, Olsovsky J, Manitius J, Fedele D, Czekalski S, Perusicova J, Skrha J, Taton J, Grzeszczak W, Crepaldi G. Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: the Di.N.A.S. randomized trial. J Am Soc Nephrol. 2002 Jun;13(6):1615-25. doi: 10.1097/01.asn.0000014254.87188.e5.

Poplawska A, Szelachowska M, Topolska J, Wysocka-Solowie B, Kinalska I. Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with micro- or macroalbuminuria. Diabetes Res Clin Pract. 1997 Nov;38(2):109-14. doi: 10.1016/s0168-8227(97)00096-x.

• Responsible Party: endocrinology department of the first affiliated hospital of Sun Yat-sen University, Yanbing Li
• ClinicalTrials.gov Identifier: NCT01316068
• Other Study ID Numbers: sulodexide20110311
• First Posted: March 16, 2011
• Last Update Posted: March 16, 2011
• Last Verified: August 2010

Keywords provided by Sun Yat-sen University:

diabetic nephropathy; albuminuria; type 2 diabetes; sulodexide

Additional relevant MeSH terms:

Kidney Diseases; Diabetic Nephropathies; Albuminuria; Urologic Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Proteinuria; Urination Disorders; Urological Manifestations; Glucuronyl glucosamine glycan sulfate; Anticoagulants; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Hypoglycemic Agents; Physiological Effects of Drugs