Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02497300 |
Other study ID # |
F140508008 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
March 2015 |
Est. completion date |
July 2021 |
Study information
Verified date |
November 2022 |
Source |
University of Alabama at Birmingham |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
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.