Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
|ClinicalTrials.gov Identifier: NCT01853553|
Recruitment Status : Completed
First Posted : May 15, 2013
Results First Posted : August 20, 2019
Last Update Posted : August 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|ADPKD||Drug: Spironolactone Drug: Sugar pill||Phase 3|
Background: Cardiovascular complications are currently the major causes of mortality among patients with autosomal dominant polycystic kidney disease (ADPKD). Therefore, testing valid interventions to reduce morbidity and mortality within this population is of high priority. It is well documented that endothelial dysfunction coupled with abnormalities in markers of oxidative stress and inflammation develops early in ADPKD even before there is a significant decline in kidney function. Aldosterone levels are increased in patients with ADPKD and may contribute to cardiovascular disease by impairing endothelial function, and reducing vascular compliance. Of note, aldosterone antagonists have been shown to improve endothelial dysfunction in a number of studies in other patient populations. However, there has been no clinical interventional studies specifically targeting endothelial dysfunction in ADPKD. Our main goal is to establish the efficacy of an aldosterone antagonist (spironolactone) for treating vascular endothelial dysfunction and large elastic artery stiffness in ADPKD patients with preserve kidney function. A key secondary goal is to determine the integrative physiological (i.e., whole limb/artery to molecular) mechanisms underlying the beneficial effects of spironolactone.
- Six months of an aldosterone antagonist will increase endothelium-dependent dilation (EDD) and reduce large elastic artery stiffness in ADPKD patients with preserve kidney function.
- The improvements in EDD after aldosterone antagonist will be associated with reduced circulating and endothelial cell markers of oxidative stress and inflammation.
- The improvements in large elastic artery stiffness after aldosterone antagonist will be associated with reduced circulating and endothelial cell markers of oxidative stress and inflammation, and changes in markers of structural protein turnover.
Impact on the Field: The expected results will provide the first insight into the:
- Efficacy of an aldosterone antagonist for the primary treatment of vascular dysfunction in ADPKD patients with preserve kidney function.
- Cellular and molecular physiological mechanisms by which these treatment benefits are conferred.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney|
|Study Start Date :||July 2013|
|Actual Primary Completion Date :||January 2017|
|Actual Study Completion Date :||January 2017|
Blood pressure medication.
Placebo Comparator: Sugar Pill
Drug: Sugar pill
- Change From Baseline in Flow Mediated Dilation at 6 Months. [ Time Frame: Baseline and 6 months. ]FMD will be determined using high-resolution ultrasonography
- Change From Baseline in Vascular Stiffness at 6 Months. [ Time Frame: Baseline and 6 months ]Aortic pulse wave velocity, a measure of large elastic arterial stiffness, and carotid compliance, a measure of large artery distensibility, will be determined. A transcutaneous custom tonometers (Noninvasive Hemodynamics Workstation, Cardiovascular Engineering Inc., Norwood, MA) will be positioned at the aorta and femoral artery to measure pulse wave velocity, and carotid artery compliance (and the β-stiffness index, a more blood pressure independent measure of local arterial stiffness) will be measured non-invasively using simultaneous high-resolution ultrasonography and applanation tonometry). Higher values correspond to greater stiffness.
- Change in Circulating Markers of Oxidative Stress at 6 Months. [ Time Frame: Baseline and 6 months. ]All markers of oxidative stress will be assayed by multiplexed validated liquid chromatography (LC)/ LC-mass spectrometry (MS)/ MS.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01853553
|United States, Colorado|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Michel B Chonchol, MD||University of Colorado, Denver|