Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Add-On

• Status: Unknown status
• Trial end date: 2018-07-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospitals Cleveland Medical Center
• Collaborator: Relypsa, Inc.
• Treatments: Mineralocorticoids; Spironolactone

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