Phase 2
N=19
Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease
Chronic Kidney Disease · Albuminuria
Bottom Line
View on ClinicalTrials.gov: NCT02497300 ↗Enrolled (actual)
19
Serious AEs
0.0%
Results posted
Dec 2022
Primary outcome: Primary: Difference in 24 Hour Ambulatory Systolic Blood Pressure — 7.7; 12.5 mm Hg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Spironolactone (Drug); Amiloride (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Alabama at Birmingham
- Primary completion
- Jul 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Difference in 24 Hour Ambulatory Systolic Blood Pressure |
7.7; 12.5 | — |
| PRIMARY Change in Oxidative Stress as Measured by Urine Levels of F2-isoprostanes |
-2.77; -0.17 | — |
| PRIMARY Change in Albuminuria |
129; 285 | — |
| SECONDARY Change in Serum Potassium |
0.4; -0.5 | — |
| SECONDARY Change in Serum Creatinine (Baseline - Post-medication) |
0.2; -0.1 | — |
Summary
Vascular endothelial dysfunction increases cardiovascular (CV) risk and contributes to the progression of chronic kidney disease (CKD). Mineralocorticoid receptor (MR) antagonists have been shown to improve endothelial function, as well as decrease CV mortality and proteinuria. The specific biochemical pathways that produce these pharmacological effects for MR antagonists, however, are poorly understood. This study investigates the effect of MR antagonism on endothelial function in patients with moderate (stage III) CKD using a randomized, controlled trial. Three specific aims are proposed: Aim 1: To determine if spironolactone improves endothelial function as compared to amiloride in patients with stage III CKD; Aim 2: To determine if oxidative stress is associated with changes in endothelial function by spironolactone compared to amiloride in patients with stage III CKD; and Aim 3: To determine if endothelial dysfunction contributes to albuminuria in patients with stage III CKD. The clinical relevance is to improve understanding of the mechanisms of kidney function decline in CKD in order to develop interventions to delay or prevent dialysis, which would translate into alleviating patient suffering, caregiver burden, and health care costs.
Eligibility Criteria
Inclusion Criteria
- Adults (18-65 years of age)
- CKD (eGFR 25-60 mL/min/1.73m2) with urine albumin-to-creatinine ratio > 30 mg/g
- CKD (eGFR > 60 mL/min/1.73m2) with urine albumin-to-creatinine ratio ≥ 300 mg/g
Exclusion Criteria
- Severe hypertension (HTN) (office BP ≥ 160/100 mm Hg)
- Hypotension (office BP 5 milliequivalent/L
- History of arrhythmia, including atrial fibrillation
- Pregnant or breast feeding woman
- Diabetes mellitus (DM) type 1
- Diabetes mellitus type 2 with glycosylated hemoglobin ≥ 6.5%
- Dementia or cognitive impairment prohibiting consent
- History of ischemic stroke, unstable angina, or myocardial infarction within the past 6 months
- Allergy or intolerance to spironolactone or amiloride
- Use of an MR antagonist or an epithelial sodium channel blocking medication within the last month
- Known primary aldosteronism or renal artery stenosis
Data sourced from ClinicalTrials.gov (NCT02497300). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.