Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Condition: ADPKD
MeSH terms: Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Interventional
Phase: Phase 3

Summary: 
      The proposed research will determine the effectiveness of blocking aldosterone for improving
      the health and function of arteries in patients with autosomal dominant polycystic kidney
      disease (ADPKD). The study also will provide insight into how blocking aldosterone improves
      artery health by determining the physiological mechanisms (biological reasons) involved.
      Overall, the proposed research will provide important new scientific evidence upon which
      physicians can base recommendations to patients with ADPKD to decrease risk of developing
      cardiovascular diseases.
    

Detailed description: 
      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.

      Working Hypotheses:

        1. 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.

        2. The improvements in EDD after aldosterone antagonist will be associated with reduced
           circulating and endothelial cell markers of oxidative stress and inflammation.

        3. 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.
    

Intervention name(s): Spironolactone; Sugar pill
Intervention type(s): Drug; Drug
Intervention description(s): Blood pressure medication.; Placebo.
Intervention MeSH terms: Spironolactone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment