Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial
Condition: Atherosclerosis
MeSH terms: Atherosclerosis
Intervention: Spironolactone; Placebo
Intervention description: 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.; Placebo
Intervention MeSH terms: Spironolactone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 79.0
Sex: All
Minimum age: 41 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.