Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis (MIRACULOUS) Trial

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by University of Maryland
Sponsor:
Information provided by (Responsible Party):
Sanjay Rajagopalan, University of Maryland
ClinicalTrials.gov Identifier:
NCT02169089
First received: June 18, 2014
Last updated: NA
Last verified: June 2014
History: No changes posted
  Purpose

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 Eplerenone 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.

Eplerenone 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 Eplerenone in people with diabetes and atherosclerotic disease.


Condition Intervention Phase
Atherosclerosis
Drug: Eplerenone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis (MIRACULOUS) Trial

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Percent change in atheroma volume (PAV) in the thoracic aorta of Eplerenone vs. placebo [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Central aortic blood pressure of Eplerenone vs. placebo. [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
  • 24-hour mean systolic blood pressure of Eplerenone vs. placebo [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
  • Pulse wave velocity (PWV) of Eplerenone vs. placebo [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
  • Measures of insulin resistance (HOMA-IR) of Eplerenone vs. placebo [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: June 2014
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eplerenone
Eplerenone
Drug: Eplerenone
Patients will be given Eplerenone 25 mg on week 0 (visit 2). Patients will be escalated to 50 mg bid Eplerenone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.
Other Name: Inspra
Placebo Comparator: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   56 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients > 55 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 >55 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02169089

Contacts
Contact: Kylene Broadwater kbroadwater1@medicine.umaryland.edu

Locations
United States, Maryland
University of Maryland Not yet recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Sanjay Rajagopalan, MD         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Sanjay Rajagopalan, MD University of Maryland
  More Information

No publications provided

Responsible Party: Sanjay Rajagopalan, Division Head, Cardiovascular Medicine; Melvin Sharoky Endowed Professor in Cardiovascular Medicine, and Co-Director, University of Maryland Heart Center, University of Maryland
ClinicalTrials.gov Identifier: NCT02169089     History of Changes
Other Study ID Numbers: 57047
Study First Received: June 18, 2014
Last Updated: June 18, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Arterial Occlusive Diseases
Cardiovascular Diseases
Vascular Diseases
Eplerenone
Mineralocorticoids
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014