Overview

This trial is active, not recruiting.

Condition adpkd
Treatments spironolactone, sugar pill
Sponsor University of Colorado, Denver
Collaborator National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date July 2013
End date December 2016
Trial size 60 participants
Trial identifier NCT01853553, 13-1440

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Active arm
spironolactone
(Placebo Comparator)
Placebo
sugar pill

Primary Outcomes

Measure
Change from baseline in Flow mediated dilation at 6 months.
time frame: Baseline and 6 months.

Secondary Outcomes

Measure
Change from baseline in vascular stiffness at 6 months.
time frame: Baseline and 6 months

Eligibility Criteria

Male or female participants from 30 years up to 79 years old.

Inclusion Criteria: - Aged 30-79 years; - Adults with ADPKD diagnosis based on Ravine criteria aged ≥ 30 years - Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 - Hypertension defined as a systolic BP > 130 mm Hg and/or diastolic BP > 80 mmHg based on 3 separate measurements within the past year and currently on a minimum dose of an angiotensin converting enzyme inhibitor (minimum dose 10 mg P.O qd) or angiotensin receptor blocker (i.e., Losartan 25 mg P.O qd) - If using antioxidants and/or omega-3 fatty acids, must discontinue 4 weeks prior to participation - Free from alcohol dependence or abuse - Mini-mental state examination score ≥ 24; ability to provide informed consent - BMI < 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients) - Not taking medications that interact with agents administered during experimental sessions (e.g., sildenafil interacts with nitroglycerin) - Use of birth control in women of childbearing potential Exclusion Criteria: - • Average serum potassium >5.5 millequivalents or any single serum potassium > 6.0 millequivalents within the previous 6 months - Receiving an aldosterone antagonist within the previous 6 months - Use of a potassium sparing diuretic - Uncontrolled hypertension - History of liver disease - History of heart failure (EF < 35%) - History of hospitalizations within the last 3 months - Active infection or antibiotic therapy - Warfarin use - Immunosuppressive therapy within the last year - Pregnancy

Additional Information

Official title Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney
Principal investigator Michel B Chonchol, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by University of Colorado, Denver.