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Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

This study is currently recruiting participants.
Verified August 2017 by Matthew Weir, University of Maryland
ClinicalTrials.gov Identifier:
First Posted: June 20, 2014
Last Update Posted: August 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Matthew Weir, University of Maryland

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.

Condition Intervention Phase
Atherosclerosis Drug: Spironolactone Drug: Placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

Resource links provided by NLM:

Further study details as provided by Matthew Weir, University of Maryland:

Primary Outcome Measures:
  • Percent change in atheroma volume (PAV) in the thoracic aorta of Spironolactone vs. placebo [ Time Frame: 56 weeks ]

Secondary Outcome Measures:
  • Central aortic blood pressure of Spironolactone vs. placebo. [ Time Frame: 56 weeks ]
  • 24-hour mean systolic blood pressure of Spironolactone vs. placebo [ Time Frame: 56 weeks ]
  • Pulse wave velocity (PWV) of Spironolactone vs. placebo [ Time Frame: 56 weeks ]
  • Measures of insulin resistance (HOMA-IR) of Spironolactone vs. placebo [ Time Frame: 56 weeks ]

Estimated Enrollment: 130
Study Start Date: January 2016
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Spironolactone
Drug: Spironolactone
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.
Other Name: Aldactone
Placebo Comparator: Placebo
Drug: Placebo


Information from the National Library of Medicine

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Ages Eligible for Study:   46 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female patients > 45 years 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.
  2. Patients with Type II Diabetes with HbA1c ≤ 8.0 on stable anti-glycemic regimen that may include oral and/or injectable therapy (GLP-1/Insulin etc.). No new drugs are allowed. Changes in dose of glycemic regimen is allowed during the course of the trial if felt to be clinically appropriate.
  3. In addition to Type II diabetes, 2 of the following additional high risk features:

    1. Established cardiovascular disease [previous MI, CVA or PAD OR prior intervention/surgery for these conditions
    2. Age >45 years
    3. Evidence of proteinuria (Urine Albumin/Creatinine Ratio of >30) in a urine specimen within 12 months
    4. Evidence of documented retinopathy
    5. LVH on Echocardiogram or 12-lead EKG
    6. Family history of premature CAD
  4. LDL cholesterol <130 mg/dL and Plasma triglycerides <300 mg/dl
  5. Blood pressure ≤145/90 mm Hg at visit 2 (see TABLE 2)
  6. Patients must be on ACE and/or ARB therapy and statin therapy with no planned dose adjustments.
  7. Willing to sign an informed consent form to participate in the research trial

Exclusion Criteria:

  1. Uncontrolled hypertension (SBP>160 and/or DBP>95 mmHg at visit 0 (screening) and SBP >145 mm Hg at visit 2).
  2. GFR (MDRD) of <40 at Visit 1.
  3. Hyperkalemia defined as serum K+≥ 5.0 meq/L at visit 0 (screening). If K+ is >5.5 meq/L at any time point during dose escalation the patient will be terminated. If K between 5.0-5.4 meq/L, Epl dose will be decreased and K+ rechecked. If K+ continues to be ≥5.5 the patient will be discontinued from the trial. There is a specific K+ management protocol in the Human Subjects section. K+ values and management will be blinded from the study investigator.
  4. Contraindications to MRI (metallic implants, severe claustrophobia).
  5. 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.
  6. Evidence of a secondary form of hypertension.
  7. Initiation of new therapy with statins, ACEI/ARB, anti-oxidants, CCBs, diuretics, β blockers.
  8. Initiation of new therapy with GLP-1 agonists such as Liraglutide, Exenatide etc.
  9. Type I diabetes mellitus
  10. Known contraindication, including history of allergy to Epl
  11. Any surgical or medical condition which might alter pharmacokinetics of drug.
  12. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
  13. Significant hyponatremia defined as Na <130 meq/L.
  14. History of prior malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer).
  15. History of any severe, life-threatening disease.
  16. 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.
  17. History of drug abuse within the last 2 years, noncompliance and unwillingness/inability to consent.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02169089

Contact: Jeanine Brown jebrown@som.umaryland.edu

United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Matthew Weir, MD         
Sponsors and Collaborators
University of Maryland
Principal Investigator: Matthew Weir Director, Division of Nephrology
  More Information

Responsible Party: Matthew Weir, Director, Division of Nephrology, University of Maryland
ClinicalTrials.gov Identifier: NCT02169089     History of Changes
Other Study ID Numbers: 57047
First Submitted: June 18, 2014
First Posted: June 20, 2014
Last Update Posted: August 24, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents