Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease
Information source: University of Alabama at Birmingham
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Kidney Disease; Albuminuria
Intervention: Spironolactone (Drug); Amiloride (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: University of Alabama at Birmingham Overall contact: Eric Judd, MD, Phone: 205 996-2186, Email: ejudd@uab.edu
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.
Clinical Details
Official title: Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Percent change in flow-mediated dilationChange in oxidative stress as measured by urine levels of F2-isoprostanes Change in albuminuria
Secondary outcome: Change in serum potassiumChange in estimated glomerular filtration rate
Detailed description:
Study participants with proteinuric, stage III CKD will be randomly assigned in a
double-masked fashion to spironolactone 25mg daily or amiloride 5 mg daily for 6 weeks and
then crossed over to the alternate study medication after a 1 month wash-out period.
Vascular function will be assessed at baseline and the end of each 6 week treatment period
by: 1) ultrasound guided flow-mediated dilation (FMD) of the brachial artery, 2) impedence
cardiography, 3) pulse-wave velocity, 4) 24 hour ambulatory blood pressure monitoring, and
5) serum and urine biomarkers. Participants will undergo a total of 7 visits over 16-18
weeks; 3 of the 7 visits will involve vascular function testing.
A study visit where vascular function testing is to be performed will begin at 0800 in the
morning and start with a vital sign assessment including height, weight, body fat percent,
and left arm automated BP measurement followed by confirmation of fasting status and a brief
past medical history. Each participant will then lie supine for 10 minutes in preparation
for vascular function testing. Following the pulse wave velocity, impedence cardiography,
and FMD measurements, the participant will have his/her blood and urine collected for
laboratory testing. Laboratory testing will include ~20 mL of blood for plasma and serum
testing. Participants will return 24 hour urine samples and have a 24 hour ambulatory
monitor placed. This entire visit is expected to take 2 hours.
Study visits where vascular function testing will not be performed (e. g., screening visit,
visit 2, visit 4, and visit 5; should last 30 minutes and involve a medication assessment,
vital sign check, and blood collection for serum potassium (~4 mL of blood).
All study medication will be prepared by the the University of Alabama (UAB) Research
Pharmacy in matching capsules and placed in pill bottles labeled "A" and "B". The order of
medication dispensing will follow simple randomization using an a priori randomization list
prepared by the research pharmacy. All study personnel with participant interaction are
masked to the order of study medication.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Adults (18-65 years of age)
- CKD stage III (eGFR 30-60 mL/min/1. 73m2 by 4 variable MDRD formula)
- Urine albumin-to-creatinine ratio (ACR) ≥ 30 mg/g
Exclusion Criteria:
- Severe hypertension (HTN) (office BP ≥ 160/100 mm Hg)
- Hypotension (office BP < 110/70 mm Hg)
- Serum potassium > 5 milliequivalent/L
- History of arrhythmia, including atrial fibrillation
- Pregnant or breast feeding woman
- Diabetes mellitus (DM) type 1 and type 2 or 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
Locations and Contacts
Eric Judd, MD, Phone: 205 996-2186, Email: ejudd@uab.edu
Hypertension Research Clinic at UAB, Birmingham, Alabama 35294, United States; Recruiting Felice Cook, Phone: 205-934-9281, Email: fycook@uab.edu Nikki Ware, Phone: 205 934-9281, Email: mware@uab.edu Eric Judd, MD, Principal Investigator
Additional Information
Starting date: March 2015
Last updated: July 9, 2015
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