Chronic Kidney DiseasePhase 2VEMAKDNCT02497300
Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease
A Phase 2 study testing Spironolactone and Amiloride in people with Chronic Kidney Disease and Albuminuria, run by University of Alabama at Birmingham at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Kidney Disease, Albuminuria
- What is being tested?
- Spironolactone and Amiloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Hypertension Research Clinic at UAB
Birmingham, Alabama, 35294
About this study
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.
Read the 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.
- Conditions
- Chronic Kidney Disease, Albuminuria
- Being tested
- Spironolactone, Amiloride
- Keywords
- Mineralocorticoid Receptor Antagonists, Mineralocorticoid Effects
- Medical subject headings
- Renal Insufficiency, Chronic, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
AmilorideDrug
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Experimental | Participants will be randomized to spironolactone 25mg daily for the 1st or 2nd 6 week treatment period. Receives: Drug: Spironolactone |
| Amiloride | Active comparator | Participants will be randomized to amiloride 5mg daily for the 1st or 2nd 6 week treatment period. Receives: Drug: Amiloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in 24 Hour Ambulatory Systolic Blood Pressure
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.
Measured: 6 weeks
Change in Oxidative Stress as Measured by Urine Levels of F2-isoprostanes
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.
Measured: 6 weeks
Change in Albuminuria
Change of the urine albumin-to-creatinine ratio (baseline - post-study med) after 6 weeks of spironolactone vs. 6 weeks of amiloride.
Measured: 6 weeks
Secondary outcomes (2)
Change in Serum Potassium
Difference in serum potassium levels (baseline - post-medication) after 6 weeks of spironolactone vs. 6 weeks of amiloride.
Measured: 6 weeks
Change in Serum Creatinine (Baseline - Post-medication)
Difference in serum creatinine (baseline - post-medication) after 6 weeks of spironolactone vs. 6 weeks of amiloride.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2015 (estimated)
- Study startMar 2015
- Primary completionJul 2021
- Study completionJul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Eric Judd, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02497300
- Sponsor's protocol ID
- F140508008
- Acronym
- VEMAKD
- Status last verified
- Nov 2022
- First submitted
- 8 Jul 2015
- Last updated
- 21 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vascular Effects of Mineralocorticoid Receptor Antagonism in Kidney Disease
- ClinicalTrials.gov ID
- NCT02497300
- Acronym / sponsor ID
- VEMAKD / F140508008
- Conditions
- Chronic Kidney Disease, Albuminuria
- Keywords
- Mineralocorticoid Receptor Antagonists, Mineralocorticoid Effects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Mar 2015 (actual)
- Primary completion
- Jul 2021 (actual)
- Study completion
- Jul 2021 (actual)
- First posted
- 14 Jul 2015 (estimated)
- Results
- Posted 21 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Experimental | Drug: SpironolactoneParticipants will be randomized to spironolactone 25mg daily for the 1st or 2nd 6 week treatment period. |
| Amiloride | Active comparator | Drug: AmilorideParticipants will be randomized to amiloride 5mg daily for the 1st or 2nd 6 week treatment period. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spironolactone | Drug | Spironolactone |
| Amiloride | Drug | Amiloride |
Primary outcome
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.
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.
Change in Albuminuria
Time frame: 6 weeks
Change of the urine albumin-to-creatinine ratio (baseline - post-study med) after 6 weeks of spironolactone vs. 6 weeks of amiloride.
2 secondary outcomes
Change in Serum Potassium
Time frame: 6 weeks
Change in Serum Creatinine (Baseline - Post-medication)
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Spironolactone and Amiloride in people with Chronic Kidney Disease and Albuminuria, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in 24 Hour Ambulatory Systolic Blood Pressure (time frame: 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2022.