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Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

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. Identifier: NCT02169089
Recruitment Status : Recruiting
First Posted : June 20, 2014
Last Update Posted : March 7, 2018
University of Maryland, College Park
University of Toronto
Winthrop University
Information provided by (Responsible Party):
Sanjay Rajagopalan, University Hospitals Cleveland Medical Center

Brief 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. 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 or disease Intervention/treatment Phase
Atherosclerosis Drug: Spironolactone Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
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
Study Start Date : January 2016
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Atherosclerosis

Arm Intervention/treatment
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

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

Secondary Outcome Measures :
  1. Central aortic blood pressure of Spironolactone vs. placebo. [ Time Frame: 56 weeks ]
  2. 24-hour mean systolic blood pressure of Spironolactone vs. placebo [ Time Frame: 56 weeks ]
  3. Pulse wave velocity (PWV) of Spironolactone vs. placebo [ Time Frame: 56 weeks ]
  4. Measures of insulin resistance (HOMA-IR) of Spironolactone vs. placebo [ Time Frame: 56 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   41 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Patients must be on ACE and/or ARB therapy with no planned dose adjustments.

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 <15 at Visit 0 (screening).
  3. Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening).
  4. LDL cholesterol >150 mg/dl.
  5. Plasma triglycerides >400 mg/dl.
  6. Contraindications to MRI (metallic implants, severe claustrophobia).
  7. 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.
  8. Evidence of a secondary form of hypertension.
  9. Initiation of new therapy with statins, ACEI/ARB, anti-oxidants, CCBs, diuretics, β blockers.
  10. Type I diabetes mellitus
  11. Known contraindication, including history of allergy to Spironolactone.
  12. . Any surgical or medical condition which might alter pharmacokinetics of drug (e.g. renal transplant, liver failure, liver transplant).
  13. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
  14. Significant hyponatremia defined as Na <130 meq/L.
  15. History of prior malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer).
  16. History of any severe, life-threatening disease.
  17. 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.
  18. History of drug abuse within the last 2 years, noncompliance and unwillingness/inability to consent.
  19. Pregnant women and nursing mothers.
  20. Class III or IV Congestive Heart Failure.
  21. Primary Hyperaldosteronism.

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 identifier (NCT number): NCT02169089

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Contact: Heather Conger 216-866-6550
Contact: Steven Sawicki 216-844-7188

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United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Heather Conger    216-866-6550   
Contact: Steven Sawicki    216-844-7188   
Principal Investigator: Sanjay Rajagopalan, MD         
Sub-Investigator: Mirela Dobre, MD         
Sponsors and Collaborators
University Hospitals Cleveland Medical Center
University of Maryland, College Park
University of Toronto
Winthrop University
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Principal Investigator: Sanjay Rajagopalan Chief, Cardiovascular Medicine
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Responsible Party: Sanjay Rajagopalan, Chief, Cardiovascular Medicine, University Hospitals Cleveland Medical Center Identifier: NCT02169089    
Other Study ID Numbers: 57047
First Posted: June 20, 2014    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018
Additional relevant MeSH terms:
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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