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Sponsors and Collaborators: |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Merck |
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Information provided by: | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
ClinicalTrials.gov Identifier: | NCT00067990 |
Chronic allograft nephropathy continues to be a major cause of kidney transplant loss and return to dialysis. Treatment options are limited and the course of the disease tends to be progressive. This trial is designed to prevent a major mediator of this process, namely the expansion of the cortical interstitial compartment of the kidney where most of the scarring occurs. The drug being studied, Losartan, has proven efficacious in a number of kidney diseases.
Condition | Intervention | Phase |
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Kidney Disease Proteinuria |
Drug: Losartan |
Phase IV |
Study Type: | Interventional |
Study Design: | Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Angiotensin II Blockade for the Prevention of Cortical Interstitial Expansion and Graft Loss in Kidney Transplant Recipients |
Enrollment: | 153 |
Study Start Date: | December 2002 |
Estimated Study Completion Date: | May 2012 |
Estimated Primary Completion Date: | March 2012 (Final data collection date for primary outcome measure) |
Renal transplant loss due to chronic allograft nephropathy (CAN) is widely acknowledged as a major problem that has increased in relative importance as the incidence of early graft loss from acute rejection has declined. Studies from various centers, including the University of Minnesota, suggest that, after excluding patients dying with a functioning graft, as many as 80% of patients who will return to dialysis do so because of CAN. At the present time there are no therapeutic options once the clinical manifestations of CAN have developed. Testing measures to prevent CAN have not been addressed.
The overall purpose of this project is to investigate the role of the renin-angiotensin-aldosterone system (RAAS) in the development of CAN. This system plays an important role in the progression of many experimental and clinical renal diseases. Furthermore, blockade of this system with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers has yielded beneficial results in retarding injury and progression in numerous intrinsic renal diseases. This study specifically investigates the long term benefit of the angiotensin II receptor blocker, losartan, in the prevention of cortical interstitial volume expansion (an accurate predictor of long term graft function) and graft loss from biopsy proven CAN in a 5 year, randomized, double masked, placebo controlled study of kidney transplant recipients. This clinical trial will directly test the hypothesis that blockade of the renin angiotensin aldosterone system will provide a substantial benefit through blood pressure lowering independent mechanisms, namely, interruption of fibrogenic pathways, anti-proteinuric actions, amelioration of hyperfiltration and possibly some immunomodulatory effects.
The proposed studies will also characterize the interstitial ultrastructural compositional changes that occur in the renal allografts with CAN, the effects of treatment on these changes and provide a complete description of the incidence and predictors for the development of transplant glomerulopathy. These studies will also determine the impact of angiotensin II receptor blockade on the rate of decline of glomerular filtration rate, as well as the impact of glomerular size on the rate of graft loss from CAN, the incidence and the progression of post transplant proteinuria, the nature of the permselectivity defects responsible for the proteinuria and will also explore the association of proteinuria with graft loss from CAN. This trial will also help construct a profile for the RAAS in the transplant recipients and explore the relationship between two genes polymorphisms, ACE and TGF-Beta, and CAN.
These studies should help to describe the natural history, nature and pathogenesis of CAN, elucidate early markers and predictors of this important disorder and, perhaps, define a safe and useful preventative strategy.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Minnesota | |
University of Minnesota | |
Minneapolis, Minnesota, United States, 55455 | |
Hennepin County Medical Center | |
Minneapolis, Minnesota, United States, 55415 |
Principal Investigator: | Hassan N. Ibrahim, M.D., M.S. | University of Minnesota |
Principal Investigator: | Bertram Kasiske, M.D. | Hennepin County Medical Center - Minneapolis |
Responsible Party: | University of Minnesota ( Hassan N. Ibrahim, M.D., M.S. / Principal Investigator ) |
Study ID Numbers: | ANGIOB (DK60706), DK60706 |
Study First Received: | September 3, 2003 |
Last Updated: | August 6, 2008 |
ClinicalTrials.gov Identifier: | NCT00067990 History of Changes |
Health Authority: | United States: Federal Government |
chronic allograft nephropathy post transplant proteinuria |
Angiotensin II Type 1 Receptor Blockers Signs and Symptoms Losartan Proteinuria Urologic Diseases Urination Disorders |
Vasoconstrictor Agents Anti-Arrhythmia Agents Cardiovascular Agents Kidney Diseases Antihypertensive Agents Angiotensin II |
Losartan Molecular Mechanisms of Pharmacological Action Urination Disorders Cardiovascular Agents Antihypertensive Agents Angiotensin II Pharmacologic Actions Angiotensin II Type 1 Receptor Blockers |
Urological Manifestations Signs and Symptoms Proteinuria Urologic Diseases Therapeutic Uses Vasoconstrictor Agents Kidney Diseases Anti-Arrhythmia Agents |