ADPKDPhase 3NCT01853553
Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
A Phase 3 study testing Spironolactone and Sugar pill in people with ADPKD, run by University of Colorado, Denver at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 20 to 55 years
- Conditions the study is for
- ADPKD
- What is being tested?
- Spironolactone and Sugar pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Jan 2017
- Phase
- Phase 3
- 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 20 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 20-55 years;
- Adults with ADPKD diagnosis based on Ravine criteria aged ≥ 30 years
- Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2
- Hypertension defined as a systolic BP > 130 mm Hg and/or diastolic BP > 80 mmHg based on 3 separate measurements within the past year and currently on a minimum dose of an angiotensin converting enzyme inhibitor (minimum dose 10 mg P.O qd) or angiotensin receptor blocker (i.e., Losartan 25 mg P.O qd)
- If using antioxidants and/or omega-3 fatty acids, must discontinue 4 weeks prior to participation
- Free from alcohol dependence or abuse
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- Mini-mental state examination score ≥ 24; ability to provide informed consent
- BMI < 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients)
- Not taking medications that interact with agents administered during experimental sessions (e.g., sildenafil interacts with nitroglycerin)
Who cannot join
- • Average serum potassium >5.5 millequivalents or any single serum potassium > 6.0 millequivalents within the previous 6 months
- Receiving an aldosterone antagonist within the previous 6 months
- Use of a potassium sparing diuretic or any other drug that could contribute to hyperkalemia
- Uncontrolled hypertension
- Current smokers or history of smoking in the past 12 months
- History of liver disease
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- History of heart failure (EF < 35%)
- History of hospitalizations within the last 3 months
- Active infection or antibiotic therapy
- Warfarin use
- Immunosuppressive therapy within the last year
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney
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.
Read the detailed description
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:
- Six months of an aldosterone antagonist will increase endothelium-dependent dilation (EDD) and reduce large elastic artery stiffness in ADPKD patients with preserve kidney function.
- The improvements in EDD after aldosterone antagonist will be associated with reduced circulating and endothelial cell markers of oxidative stress and inflammation.
- The improvements in large elastic artery stiffness after aldosterone antagonist will be associated with reduced circulating and endothelial cell markers of oxidative stress and inflammation, and changes in markers of structural protein turnover.
Impact on the Field: The expected results will provide the first insight into the:
- Efficacy of an aldosterone antagonist for the primary treatment of vascular dysfunction in ADPKD patients with preserve kidney function.
- Cellular and molecular physiological mechanisms by which these treatment benefits are conferred.
- Conditions
- ADPKD
- Being tested
- Spironolactone, Sugar pill
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
Blood pressure medication.
Sugar pillDrug
Placebo.
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Experimental | Active arm Receives: Drug: Spironolactone |
| Sugar Pill | Placebo comparator | Placebo Receives: Drug: Sugar pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Flow Mediated Dilation at 6 Months.
FMD will be determined using high-resolution ultrasonography
Measured: Baseline and 6 months.
Secondary outcomes (1)
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.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startJul 2013
- Primary completionJan 2017
- Study completionJan 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ADPKDStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michel B Chonchol, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01853553
- Sponsor's protocol ID
- 13-1440
- Other IDs
- R01DK097081
- Status last verified
- Aug 2019
- First submitted
- 8 May 2013
- Last updated
- 20 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- Individual data sharing
- No
Publications
Nowak KL, Gitomer B, Farmer-Bailey H, Wang W, Malaczewski M, Klawitter J, You Z, George D, Patel N, Jovanovich A, Chonchol M. Mineralocorticoid Antagonism and Vascular Function in Early Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Trial. Am J Kidney Dis. 2019 Aug;74(2):213-223. doi: 10.1053/j.ajkd.2018.12.037. Epub 2019 Feb 23.
PubMed 30803706
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney
- ClinicalTrials.gov ID
- NCT01853553
- Acronym / sponsor ID
- 13-1440
- Conditions
- ADPKD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2013
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Posted 20 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Six months of an aldosterone antagonist will increase endothelium-dependent dilation (EDD) and reduce large elastic artery stiffness in ADPKD patients with preserve kidney function.
- The improvements in EDD after aldosterone antagonist will be associated with reduced circulating and endothelial cell markers of oxidative stress and inflammation.
- The improvements in large elastic artery stiffness after aldosterone antagonist will be associated with reduced circulating and endothelial cell markers of oxidative stress and inflammation, and changes in markers of structural protein turnover.
Impact on the Field: The expected results will provide the first insight into the:
- Efficacy of an aldosterone antagonist for the primary treatment of vascular dysfunction in ADPKD patients with preserve kidney function.
- Cellular and molecular physiological mechanisms by which these treatment benefits are conferred.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Experimental | Drug: SpironolactoneActive arm |
| Sugar Pill | Placebo comparator | Drug: Sugar pillPlacebo |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Aged 20-55 years;
- Adults with ADPKD diagnosis based on Ravine criteria aged ≥ 30 years
- Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2
- Hypertension defined as a systolic BP > 130 mm Hg and/or diastolic BP > 80 mmHg based on 3 separate measurements within the past year and currently on a minimum dose of an angiotensin converting enzyme inhibitor (minimum dose 10 mg P.O qd) or angiotensin receptor blocker (i.e., Losartan 25 mg P.O qd)
- If using antioxidants and/or omega-3 fatty acids, must discontinue 4 weeks prior to participation
Key exclusion criteria (12 listed)
- • Average serum potassium >5.5 millequivalents or any single serum potassium > 6.0 millequivalents within the previous 6 months
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 |
|---|---|---|
| SpironolactoneBlood pressure medication. | Drug | Spironolactone |
| Sugar pillPlacebo. | Drug | Sugar Pill |
Primary outcome
Change From Baseline in Flow Mediated Dilation at 6 Months.
Time frame: Baseline and 6 months.
FMD will be determined using high-resolution ultrasonography
1 secondary outcome
Change From Baseline in Vascular Stiffness at 6 Months.
Time frame: Baseline and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30803706Nowak KL, Gitomer B, Farmer-Bailey H, Wang W, Malaczewski M, Klawitter J, You Z, George D, Patel N, Jovanovich A, Chonchol M. Mineralocorticoid Antagonism and Vascular Function in Early Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Trial. Am J Kidney Dis. 2019 Aug;74(2):213-223. doi: 10.1053/j.ajkd.2018.12.037. Epub 2019 Feb 23.
- Individual participant dataSharing planned: No
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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.
Michel B Chonchol, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Spironolactone and Sugar pill in people with ADPKD, run by University of Colorado, Denver 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 9 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 20 Aug 2019. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 20 Aug 2019). 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?
Change From Baseline in Flow Mediated Dilation at 6 Months. (time frame: Baseline and 6 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01853553, which also lists 1 linked publication.
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 20 Aug 2019.