A Phase 3 interventional study of Spironolactone and Sugar pill in ADPKD, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to participants aged 20 Years to 55 Years. Per ClinicalTrials.gov, last updated 2019-08-20.
Sponsored by University of Colorado, Denver · Phase 3, Interventional, and Treatment
The proposed research will determine the effectiveness of blocking aldosterone for improving the health and function of arteries in patients with autosomal dominant polycystic kidney disease (ADPKD). The study also will provide insight into how blocking aldosterone improves artery health by determining the physiological mechanisms (biological reasons) involved. Overall, the proposed research will provide important new scientific evidence upon which physicians can base recommendations to patients with ADPKD to decrease risk of developing cardiovascular diseases.
Background: Cardiovascular complications are currently the major causes of mortality among patients with autosomal dominant polycystic kidney disease (ADPKD). Therefore, testing valid interventions to reduce morbidity and mortality within this population is of high priority. It is well documented that endothelial dysfunction coupled with abnormalities in markers of oxidative stress and inflammation develops early in ADPKD even before there is a significant decline in kidney function. Aldosterone levels are increased in patients with ADPKD and may contribute to cardiovascular disease by impairing endothelial function, and reducing vascular compliance. Of note, aldosterone antagonists have been shown to improve endothelial dysfunction in a number of studies in other patient populations. However, there has been no clinical interventional studies specifically targeting endothelial dysfunction in ADPKD. Our main goal is to establish the efficacy of an aldosterone antagonist (spironolactone) for treating vascular endothelial dysfunction and large elastic artery stiffness in ADPKD patients with preserve kidney function. A key secondary goal is to determine the integrative physiological (i.e., whole limb/artery to molecular) mechanisms underlying the beneficial effects of spironolactone.
Working Hypotheses:
Impact on the Field: The expected results will provide the first insight into the:
177 studies on the registry are indexed under Polycystic Kidney, Autosomal Dominant; 39 are open to participants now.
This study's enrollment of 61 is above the median of 51 across 132 interventional studies indexed under Polycystic Kidney, Autosomal Dominant.
Browse Polycystic Kidney, Autosomal Dominant studies →University of Colorado, Denver is the lead sponsor of 1,538 studies on the registry; 319 are open to participants now.
Of its 146 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
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Exclusion Criteria:
Average serum potassium >5.5 millequivalents or any single serum potassium > 6.0 millequivalents within the previous 6 months
Active arm
Drug: Spironolactone
Placebo
Drug: Sugar pill
Blood pressure medication.
Placebo.
Change From Baseline in Flow Mediated Dilation at 6 Months.
FMD will be determined using high-resolution ultrasonography
Time frame: Baseline and 6 months.
Change From Baseline in Vascular Stiffness at 6 Months.
Aortic pulse wave velocity, a measure of large elastic arterial stiffness, and carotid compliance, a measure of large artery distensibility, will be determined. A transcutaneous custom tonometers (Noninvasive Hemodynamics Workstation, Cardiovascular Engineering Inc., Norwood, MA) will be positioned at the aorta and femoral artery to measure pulse wave velocity, and carotid artery compliance (and the β-stiffness index, a more blood pressure independent measure of local arterial stiffness) will be measured non-invasively using simultaneous high-resolution ultrasonography and applanation tonometry). Higher values correspond to greater stiffness.
Time frame: Baseline and 6 months
Change in Circulating Markers of Oxidative Stress at 6 Months.
All markers of oxidative stress will be assayed by multiplexed validated liquid chromatography (LC)/ LC-mass spectrometry (MS)/ MS.
Time frame: Baseline and 6 months.
Eligible participants were enrolled at the University of Colorado Denver Anschutz Medical Campus between July 2014 and June 2016 (the trial concluded according to enrollment determined by power calculations described below).Although Grant was awarded in 2013, recruitment did not start until 2014.
| Milestone | Spironolactone | Sugar Pill |
|---|---|---|
| Started | 29 | 32 |
| Completed | 28 | 32 |
| Not completed | 1 | 0 |
FMD will be determined using high-resolution ultrasonography
| Percent change. | Spironolactone | Sugar Pill |
|---|---|---|
| Change From Baseline in Flow Mediated Dilation at 6 Months. | -0.2 ± 3.2 | -0.4 ± 4.7 |
Aortic pulse wave velocity, a measure of large elastic arterial stiffness, and carotid compliance, a measure of large artery distensibility, will be determined. A transcutaneous custom tonometers (Noninvasive Hemodynamics Workstation, Cardiovascular Engineering Inc., Norwood, MA) will be positioned at the aorta and femoral artery to measure pulse wave velocity, and carotid artery compliance (and the β-stiffness index, a more blood pressure independent measure of local arterial stiffness) will be measured non-invasively using simultaneous high-resolution ultrasonography and applanation tonometry). Higher values correspond to greater stiffness.
| m/s | Spironolactone | Sugar Pill |
|---|---|---|
| Change From Baseline in Vascular Stiffness at 6 Months. | -37 ± 78 | -1 ± 89 |
All markers of oxidative stress will be assayed by multiplexed validated liquid chromatography (LC)/ LC-mass spectrometry (MS)/ MS.
Results for this outcome have not been posted.
Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Spironolactone | — | 0/28 (0%) | 0/28 (0%) |
| Sugar Pill | — | 0/32 (0%) | 0/32 (0%) |
| Age, Continuous(years) | Spironolactone | Sugar Pill | Total |
|---|---|---|---|
| Mean | 34 ± 10 | 34 ± 9 | 34 ± 10 |
| Sex: Female, Male(Participants) | Spironolactone | Sugar Pill | Total |
|---|---|---|---|
| Female | 13 | 20 | 33 |
| Male | 16 | 12 | 28 |
Plan to share: No
The record gives a start of Jul 2013, a primary completion of Jan 2017 and a completion of Jan 2017. It does not say whether these dates are actual or estimated.
Results were first posted in Aug 2019, 2 years 7 months after primary completion.
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This study is completed, as verified in Aug 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Spironolactone
Polycystic Kidney, Autosomal Dominant →
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