Effect of Sulodexide on Albuminuria in Chinese Type 2 Diabetic Patients

Diabetic Nephropathy Clinical Trial

— Soften  

Official title:

Effect of Intravenous and Oral Therapy With Sulodexide on Albuminuria in Type 2 Diabetic Patients

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01316068
• Other study ID #: sulodexide20110311
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: March 15, 2011
• Last updated: March 15, 2011
• Start date: March 2011
• Est. completion date: August 2012

Study information

• Verified date: August 2010
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Albuminuria
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

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.
• use of sulodexide orally only
Patients receive 1000 LSU per day orally for 52 weeks

Locations

Country	Name	City	State
China	endocrinology department of the first affiliated hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	ALFA WASSERMANN(BJ) Market Research and Management Co., Ltd

Country where clinical trial is conducted

China, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

Gambaro G, Kinalska I, Oksa A, Pont'uch P, Hertlová M, Olsovsky J, Manitius J, Fedele D, Czekalski S, Perusicová 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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2006 Dec 21. — View Citation

Weiss R, Niecestro R, Raz I. The role of sulodexide in the treatment of diabetic nephropathy. Drugs. 2007;67(18):2681-96. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in urine albumin/creatinine ratio	conversion to normoalbuminuria and at least a 25% reduction in UACR opposed to baseline, or 50% reduction in UACR opposed to baseline	52th week since the commence of therapy	No
Secondary	Change from Baseline in urine albumin/creatinine ratio and serum creatinine		before and 2nd,12th,24th,36th and 60th week since the commence of therapy	No