The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity (SPIREN)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01602861|
Recruitment Status : Unknown
Verified January 2014 by Line Aas Mortensen, Odense University Hospital.
Recruitment status was: Enrolling by invitation
First Posted : May 21, 2012
Last Update Posted : January 24, 2014
The purpose of this study is to assess whether the diuretic drug spironolactone can prevent chronic damage to transplanted kidneys caused by the medication that prevents rejection.
Spironolactone prevents the effects of the hormone aldosterone. Aldosterone is suspected of being involved in the processes leading to chronic rejection of transplanted kidneys. Hence, by blocking the effects of aldosterone we hope to be able to prevent loss of kidney function in transplant patients.
|Condition or disease||Intervention/treatment||Phase|
|Disorder Related to Renal Transplantation||Drug: Spironolactone Drug: placebo||Phase 4|
AIM: The purpose of this study is to assess whether spironolactone can prevent the formation of fibrosis in transplanted kidneys.
BACKGROUND: Calcineurin inhibitors (CNI) are one of the cornerstones of immunosuppressive therapy after kidney transplantation. The introduction of CNI has caused a significant decrease in acute rejections. However, CNI also have known side effects. These include the formation of tubulointerstitial fibrosis in the transplanted kidney, contributing over time to impaired kidney function and reduced graft survival.
The mineralocorticoid aldosterone may be involved in the development of renal fibrosis. Recent observations suggest that aldosterone plays a central role in the pathogenesis of CNI nephrotoxicity and that the mineralocorticoid-receptor-blocker spironolactone could be a useful agent to prevent it.
METHODS: This study is a randomized, placebo-controlled, double-blind study in which 170 renal transplant patients will be recruited from two nephrological departments in Southern Denmark. Patients will be randomized to three years of treatment with either spironolactone or placebo added to the standard immunosuppressive treatment. Renal graft biopsies, various molecular tests of tissue, blood and urine, chrome-EDTA clearance, 24-hour bloodpressure measurement and blood samples will be performed at inclusion, after 1 year, 2 years and upon completion.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||170 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity|
|Study Start Date :||February 2013|
|Estimated Primary Completion Date :||September 2017|
|Estimated Study Completion Date :||September 2017|
One tablet per day (25 mg Spironolactone/placebo) for the first three months. Subsequently dosage is increased to two tablets per day (50 mg Spironolactone/placebo) for the rest of the study.
In case of hyperkaliemia (>5,5 mmol/L) or intolerable side effects dosage will be reduced to one tablet per day (25 mg Spironolactone/placebo).
|Placebo Comparator: Placebo||Drug: placebo|
- Improved Cr EDTA clearance [ Time Frame: 0, 1 year, 2 years ]
- Reduced urine protein levels [ Time Frame: Every 3 months ]
- Reduced fibrosis [ Time Frame: 0, 2 years ]Verified by graft biopsies and immuno histochemistry. Newly transplanted patients will be subjected to additional biopsies 3 months and 1 year after inclusion.
- Reduced blood pressure [ Time Frame: 0, 1 year, 2 years ]
- Cardiovascular events [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01602861
|Odense University Hospital|
|Odense C, Denmark, 5000|
|Study Director:||Claus Bistrup, MD, ph.d.||Dep. of Nephrology, Odense University Hospital|