- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02497300
Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease (VEMAKD)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- Hypertension Research Clinic at UAB
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 < 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Spironolactone
Participants will be randomized to spironolactone 25mg daily for the 1st or 2nd 6 week treatment period.
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Active Comparator: Amiloride
Participants will be randomized to amiloride 5mg daily for the 1st or 2nd 6 week treatment period.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in 24 Hour Ambulatory Systolic Blood Pressure
Time Frame: 6 weeks
|
The study was not able to meet its recruitment goal, and participant numbers were too low to test the intended primary outcome of "Difference in percent change of ultrasound-guided flow-mediated dilation between 6 weeks of spironolactone vs. 6 weeks of amiloride."
The change in 24hr ABPM systolic BP (Baseline - 6 week) is reported here.
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6 weeks
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Change in Oxidative Stress as Measured by Urine Levels of F2-isoprostanes
Time Frame: 6 weeks
|
Difference in level of urine 8-iso-prostaglandin-F2-alpha per mg of creatinine levels between 6 weeks of spironolactone vs. 6 weeks of amiloride.
|
6 weeks
|
Change in Albuminuria
Time Frame: 6 weeks
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Change of the urine albumin-to-creatinine ratio (baseline - post-study med) after 6 weeks of spironolactone vs. 6 weeks of amiloride.
|
6 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Serum Potassium
Time Frame: 6 weeks
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Difference in serum potassium levels (baseline - post-medication) after 6 weeks of spironolactone vs. 6 weeks of amiloride.
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6 weeks
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Change in Serum Creatinine (Baseline - Post-medication)
Time Frame: 6 weeks
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Difference in serum creatinine (baseline - post-medication) after 6 weeks of spironolactone vs. 6 weeks of amiloride.
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6 weeks
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Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urologic Diseases
- Urological Manifestations
- Renal Insufficiency
- Urination Disorders
- Proteinuria
- Kidney Diseases
- Renal Insufficiency, Chronic
- Albuminuria
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Sodium Channel Blockers
- Hormone Antagonists
- Mineralocorticoid Receptor Antagonists
- Diuretics, Potassium Sparing
- Acid Sensing Ion Channel Blockers
- Epithelial Sodium Channel Blockers
- Spironolactone
- Amiloride
Other Study ID Numbers
- F140508008
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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