Clinical trial NCT00130208
Conditions: Diabetic Nephropathy
Keywords: Diabetes Diabetes Mellitus, Type 2 Albuminuria Diabetic Nephropathy
Sponsor: Keryx Biopharmaceuticals
Start date: 2005-08-01; Completion date: 2008-02-01
Enrollment: 1056 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to determine whether treatment with sulodexide is effective in reducing the level of urine albumin excretion in patients with early diabetic kidney disease expressed as microalbuminuria.

Detailed description:
Diabetic nephropathy is an important cause of morbidity and mortality in patients with either type 1 or type 2 diabetes mellitus. The pathogenesis and natural history of diabetic nephropathy is characterized initially by microalbuminuria followed by a progressive decline in glomerular function. An emerging body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve pathobiochemical alterations of glycoproteins in these structures. Evidence, in experimental animals rendered diabetic, reveals that the administration of heparin and other anionic glycoproteins (GAG) can effectively prevent the biochemical alterations which are responsible for albuminuria. Sulodexide, an orally active agent which does not have anticoagulant properties associated with its oral dose range, is comprised of three naturally occurring glycosaminoglycan (GAG) polysaccharide components isolated from porcine intestinal mucosa. Small clinical studies employing sulodexide, have shown that albuminuria is significantly diminished in patients with diabetic nephropathy, even when these patients are receiving angiotensin II receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI), agents already proven to reduce albuminuria and slow progressive diabetic nephropathy.

This study is designed to evaluate whether sulodexide is safe and effective in treating subjects with type 2 diabetic nephropathy. Subjects with type 2 diabetes and microalbuminuria (defined as a urinary albumin to creatinine ratio,(ACR)in men 35-200 mg/G and in women 45-200 mg/G) who are also receiving either irbesartan 300 mg/day, losartan 100 mg/day, or a maximum approved dose of an angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEI) will be enrolled in the study. The study will consist of the following periods:

* Screening: of 1-2 weeks for assessing basic eligibility/exclusion criteria
* Run-in: of up to 16 weeks on maximal dose of ARB or ACE with stable blood pressure control
* Qualifying visit: qualifying patients are on maximal dose of ARB or ACE for a minimum of 4 months with stable BP control, SBP \<150 mmHg, DBP \<90 mmHg and albumin to creatinine ratio, (ACR) between in men 35-200 mg/G and in women 45-200 average of 3 first morning voids
* Randomization: patients are randomized to sulodexide 100 mg or matching placebo administered orally twice a day.
* Maintenance: 26 week maintenance period, with 4 visits to monitor safety and ACR
* Washout Period: 8 week washout period, with 2 visits to monitor safety and ACR

Arms: arm 1: Also known as KRX-101. All patients will be on standard of care ACE or ARBs. arm 2: All patients will be on standard of care ACE or ARBs.
Interventions: intervention 1: Sulodexide intervention 2: Placebo
Intervention descriptions: intervention 1: 100 mg sulodexide gelcaps intervention 2: 0 mg gelcap

Protocol documents: