AtherosclerosisPhase 4NCT02169089
Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial
A Phase 4 study testing Spironolactone in people with Atherosclerosis, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
Atherosclerotic disease, or hardening of the arteries, is characterized by the thickening of the arterial walls due to fatty deposits in wall and inflammation in the wall of arteries. Read more about this study
- Who is it for?
- Ages 41 years and older
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- Spironolactone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 29 Apr 2022
- Phase
- Phase 4
- 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 41 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients >45 or >40 years with known atherosclerotic events (examples include MI, Stroke) and able to provide informed consent (females must be either post-menopausal for one year, surgically sterile, or using effective contraception. Oral contraceptives are disallowed.
- Patients with Type II Diabetes with HbA1c ≤ 9.0 on stable anti-glycemic regimen that may include oral and/or injectable therapy (GLP-1/Insulin etc.). Changes in dose of glycemic regimen is allowed during the course of the trial if felt to be clinically appropriate.
- GFR <90 and evidence of proteinuria (Urine albumin/creatinine ratio of >30 mg/g or equivalent) in a urine specimen within 12 months OR GFR <60 mg/g regardless of proteinuria.
- Patients must be on ACE and/or ARB therapy with no planned dose adjustments.
Who cannot join
- Uncontrolled hypertension (SBP>160 and/or DBP>95 mmHg at visit 0 (screening) and SBP >145 mm Hg at visit 2).
- GFR (MDRD) of <15 at Visit 0 (screening).
- Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening).
- LDL cholesterol >150 mg/dl.
- Plasma triglycerides >400 mg/dl.
- Contraindications to MRI (metallic implants, severe claustrophobia).
Show all 21Show fewer
- Acute coronary syndrome, Transient ischemic attack, CVA or critical limb ischemia during the last 6 months or coronary/peripheral revascularization within the last 3 months.
- Evidence of a secondary form of hypertension.
- Initiation of new therapy with statins, ACEI/ARB, anti-oxidants, CCBs, diuretics, β blockers.
- Type I diabetes mellitus
- Known contraindication, including history of allergy to Spironolactone.
- . Any surgical or medical condition which might alter pharmacokinetics of drug (e.g. renal transplant, liver failure, liver transplant).
- Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
- Significant hyponatremia defined as Na <130 meq/L.
- History of prior malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer).
- History of any severe, life-threatening disease.
- Any surgical or medical conditions which places the patient at higher risk derived from his/her participation into the study, or likely to prevent patient from complying with requirements.
- History of drug abuse within the last 2 years, noncompliance and unwillingness/inability to consent.
- Pregnant women and nursing mothers.
- Class III or IV Congestive Heart Failure.
- Primary Hyperaldosteronism.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
About this study
Atherosclerotic disease, or hardening of the arteries, is characterized by the thickening of the arterial walls due to fatty deposits in wall and inflammation in the wall of arteries. High cholesterol, high blood pressure, diabetes, obesity and genetics play an important role in developing clinical symptoms of atherosclerosis disease. The complications of advanced atherosclerosis are chronic, slowly progressive and cumulative, resulting in heart attack, stroke and/or death and blockage of arteries.
This study is being done to assess the effectiveness of Spironolactone therapy to slow down the worsening of atherosclerotic disease (hardening of the arteries) in aorta (this is a large vessel coming out of your heart) compared to placebo (look alike sugar pill). This will be checked by comparing before and after therapy magnetic resonance imaging (MRI) pictures of your aortic wall.
Spironolactone is an FDA approved drug used to treat heart failure and in the management of hypertension (high blood pressure), but in this study it is used for another unapproved reason. In this study, we would like to evaluate the effects of Spironolactone in people with diabetes and atherosclerotic disease.
- Conditions
- Atherosclerosis
- Being tested
- Spironolactone, Placebo
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
Also called Aldactone
Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Experimental | Spironolactone Receives: Drug: Spironolactone |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo
Measured: 56 weeks
Secondary outcomes (4)
Left Ventricular Mass Index of Spironolactone vs. Placebo.
Measured: 56 weeks
Myocardial Fibrosis (Change in Native T1) Spironolactone vs. Placebo
Measured: 56 weeks
Change in 24-hour Ambulatory Systolic Blood Pressure of Spironolactone vs. Placebo
Measured: 11 weeks
Measures of Insulin Resistance (HOMA-IR) of Spironolactone vs. Placebo
Measured: 56 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2014 (estimated)
- Study startJan 2016
- Primary completion29 Apr 2022
- Study completion29 Apr 2022
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 AtherosclerosisStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, University of Toronto, Winthrop University
- Responsible party
- Principal investigator, Sanjay Rajagopalan, University Hospitals Cleveland Medical Center
- Investigators
- Sanjay Rajagopalan, Principal investigator, Chief, Cardiovascular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02169089
- Sponsor's protocol ID
- 57047
- Status last verified
- Jul 2023
- First submitted
- 18 Jun 2014
- Last updated
- 1 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rajagopalan S, Dobre M, Dazard JE, Vergara-Martel A, Connelly K, Farkouh ME, Gaztanaga J, Conger H, Dever A, Razavi-Nematollahi L, Fares A, Pereira G, Edwards-Glenn J, Cameron M, Cameron C, Al-Kindi S, Brook RD, Pitt B, Weir M. Mineralocorticoid Receptor Antagonism Prevents Aortic Plaque Progression and Reduces Left Ventricular Mass and Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease: The MAGMA Trial. Circulation. 2024 Aug 27;150(9):663-676. doi: 10.1161/CIRCULATIONAHA.123.067620. Epub 2024 Aug 12.
PubMed 39129649
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial
- ClinicalTrials.gov ID
- NCT02169089
- Acronym / sponsor ID
- 57047
- Conditions
- Atherosclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Collaborators
- University of Maryland, University of Toronto, Winthrop University
- Study start
- Jan 2016 (actual)
- Primary completion
- 29 Apr 2022 (actual)
- Study completion
- 29 Apr 2022 (actual)
- First posted
- 20 Jun 2014 (estimated)
- Results
- Posted 1 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Atherosclerotic disease, or hardening of the arteries, is characterized by the thickening of the arterial walls due to fatty deposits in wall and inflammation in the wall of arteries. High cholesterol, high blood pressure, diabetes, obesity and genetics play an important role in developing clinical symptoms of atherosclerosis disease. The complications of advanced atherosclerosis are chronic, slowly progressive and cumulative, resulting in heart attack, stroke and/or death and blockage of arteries.
This study is being done to assess the effectiveness of Spironolactone therapy to slow down the worsening of atherosclerotic disease (hardening of the arteries) in aorta (this is a large vessel coming out of your heart) compared to placebo (look alike sugar pill). This will be checked by comparing before and after therapy magnetic resonance imaging (MRI) pictures of your aortic wall.
Spironolactone is an FDA approved drug used to treat heart failure and in the management of hypertension (high blood pressure), but in this study it is used for another unapproved reason. In this study, we would like to evaluate the effects of Spironolactone in people with diabetes and atherosclerotic disease.
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: SpironolactoneSpironolactone |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 41 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female patients >45 or >40 years with known atherosclerotic events (examples include MI, Stroke) and able to provide informed consent (females must be either post-menopausal for one year, surgically sterile, or using effective contraception. Oral contraceptives are disallowed.
- Patients with Type II Diabetes with HbA1c ≤ 9.0 on stable anti-glycemic regimen that may include oral and/or injectable therapy (GLP-1/Insulin etc.). Changes in dose of glycemic regimen is allowed during the course of the trial if felt to be clinically appropriate.
- GFR <90 and evidence of proteinuria (Urine albumin/creatinine ratio of >30 mg/g or equivalent) in a urine specimen within 12 months OR GFR <60 mg/g regardless of proteinuria.
- Patients must be on ACE and/or ARB therapy with no planned dose adjustments.
Key exclusion criteria (21 listed)
- Uncontrolled hypertension (SBP>160 and/or DBP>95 mmHg at visit 0 (screening) and SBP >145 mm Hg at visit 2).
- GFR (MDRD) of <15 at Visit 0 (screening).
- Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening).
- LDL cholesterol >150 mg/dl.
- Plasma triglycerides >400 mg/dl.
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 |
|---|---|---|
| SpironolactoneAlso: AldactonePatients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks. | Drug | Spironolactone |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo
Time frame: 56 weeks
4 secondary outcomes
Left Ventricular Mass Index of Spironolactone vs. Placebo.
Time frame: 56 weeks
Myocardial Fibrosis (Change in Native T1) Spironolactone vs. Placebo
Time frame: 56 weeks
Change in 24-hour Ambulatory Systolic Blood Pressure of Spironolactone vs. Placebo
Time frame: 11 weeks
Measures of Insulin Resistance (HOMA-IR) of Spironolactone vs. Placebo
Time frame: 56 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39129649Rajagopalan S, Dobre M, Dazard JE, Vergara-Martel A, Connelly K, Farkouh ME, Gaztanaga J, Conger H, Dever A, Razavi-Nematollahi L, Fares A, Pereira G, Edwards-Glenn J, Cameron M, Cameron C, Al-Kindi S, Brook RD, Pitt B, Weir M. Mineralocorticoid Receptor Antagonism Prevents Aortic Plaque Progression and Reduces Left Ventricular Mass and Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease: The MAGMA Trial. Circulation. 2024 Aug 27;150(9):663-676. doi: 10.1161/CIRCULATIONAHA.123.067620. Epub 2024 Aug 12.
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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.
Sanjay Rajagopalan principal investigator
Chief, Cardiovascular Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Spironolactone in people with Atherosclerosis, run by University Hospitals Cleveland Medical Center 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 4 inclusion and 21 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 1 Aug 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 1 Aug 2023). 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?
Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo (time frame: 56 weeks). 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 NCT02169089, 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 1 Aug 2023.