Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Add-On
Condition: Type2 Diabetes; Hyperkalemia
MeSH terms: Atherosclerosis; Hyperkalemia
Intervention: Spironolactone
Intervention description: The study participants will receive concomitant treatment with Veltassa 8.4 grams per day and Spironolactone 25 mg per day or maximum tolerated dose. If dictated by the potassium level, Veltassa can be increased to 16.8 grams per day.
Intervention MeSH terms: Spironolactone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: An open label proof-of-concept clinical trial in 50 patients with Type II diabetes evaluating the effects of MRA + Patiromer on LV mass and plaque regression over 12 months of treatment by magnetic resonance imaging (MRI).
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No

Summary:

      Patiromer add-on to a mineralocorticoid receptor antagonist (MRA) in patients with Type 2
      diabetes mellitus and chronic kidney disease (CKD) will reduce blood pressure and left
      ventricular (LV) mass to a greater extent compared to patients with MRA alone and favorably
      affect key secondary hemodynamic and inflammatory variables including atherosclerosis
      progression.

      Atherosclerosis is the leading cause of morbidity and mortality in Type II diabetes. A cell
      type called the monocyte/macrophage is critical to development and complications of
      atherosclerosis.

      This project will evaluate the effectiveness of a medication called Spironolactone in
      addition to Patiromer in preventing atherosclerosis in Type II diabetes through its effects
      on cells such as the monocyte. Spironolactone has been demonstrated to be effective for the
      treatment of patients after a heart attack and stroke. The investigators will evaluate the
      impact of Spironolactone in combination with Patiromer in reducing atherosclerosis plaque and
      additionally evaluate its potential in changing inflammation.

      The investigators envision that a strategy of simultaneously probing effect of a drug
      combined with analysis of mechanisms of action and predictive response will likely provide
      key information with which to design hard event (heart attack, stroke etc.) based trials.
    

Eligibility criteria:

        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 ≤ 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. Glomerular filtration rate (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 angiotensin-converting-enzyme inhibitor (ACE) and/or
             angiotensin-resistance-blocker (ARB) therapy with no planned dose adjustments.

          5. Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening).

        Exclusion Criteria

          1. Uncontrolled hypertension (Systolic Blood Pressure (SBP)>160 and/or Diastolic Blood
             Pressure (DBP)>95 mmHg at visit 0 (screening) and SBP >145 mm Hg at visit 2).

          2. GFR (MDRD) of <20 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, cardiovascular accident (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, ACE/ARB, antioxidants, calcium channel
             blockers (CCBs), diuretics, β blockers.

         10. Type I diabetes mellitus

         11. Known contraindication, including history of allergy to Spironolactone or Patiromer

         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 cured prostate cancer).

         16. History of any severe, life-threatening disease.

         17. Any surgical or medical conditions which place 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