Effect of Sulodexide in Early Diabetic Nephropathy
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||The Collaborative Study Group Trial: The Effect of Sulodexide in Patients With Type 2 Diabetes and Microalbuminuria|
- Conversion from microalbuminuria to normoalbuminuria [ Time Frame: 34 Weeks ] [ Designated as safety issue: No ]Run-in period, followed by a treatment period, followed by a Washout Period. Treatment period is 30 weeks and Washout Period 4 weeks.
- Greater than 50% reduction in microalbuminuria [ Time Frame: 30 Weeks ] [ Designated as safety issue: No ]During the treatment period, KRX-101 is being compared to placebo to assess whether a 50% reduction in microalbuminuria has been achieved.
- Observed change in albumin excretion [ Time Frame: 34 Weeks ] [ Designated as safety issue: No ]Review of albumin excretion during the treatment period will be made and will also be compared to albumin excretion during the washout period.
- Comparison of adverse events, laboratory parameters, and physical exams between active and placebo patients [ Time Frame: 34 weeks (also screening and run-in periods) ] [ Designated as safety issue: Yes ]Patients will be reviewed for adverse events, laboratory parameters, and physical examinations throughout the trial and compared by treatment arm (active v. placebo).
|Study Start Date:||August 2005|
|Study Completion Date:||February 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
Also known as KRX-101. All patients will be on standard of care ACE or ARBs.
Placebo Comparator: Placebo
All patients will be on standard of care ACE or ARBs.
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
|United States, Illinois|
|The Collaborative Study Group, Clinical Coordinating Center for U.S. and Canadian Clinics, Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|The Collaborative Study Group, Clinical Coordinating Center for the Pacific Region, Monash Medical Center|
|Clayton / Melbourne, Victoria, Australia, 3168|
|The Collaborative Study Group, Clinical Coordinating Center for European Clinics, University of Groningen|
|Groningen, Netherlands, 9713 AV|
|Study Director:||Edmund J Lewis, M.D.||The Collaborative Study Group, Rush University Medical Center, Chicago, IL USA|
|Principal Investigator:||Robert C Atkins, M.D.||The Collaborative Study Group, Monash Medical Center, Clayton, Victoria, AUSTRALIA|
|Principal Investigator:||Dick deZeeuw, M.D.||The Collaborative Study Group, University of Groningen, NETHERLANDS|
|Principal Investigator:||Itamar Raz, M.D.||The Collaborative Study Group, Hadassah University, Jerusalem, ISRAEL|