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Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

Primary Purpose

Atherosclerosis

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Spironolactone

Placebo

About this trial

This is an interventional treatment trial for Atherosclerosis

Eligibility Criteria

41 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Uncontrolled hypertension (SBP>160 and/or DBP>95 mmHg at visit 0 (screening) and SBP >145 mm Hg at visit 2).
GFR (MDRD) of <15 at Visit 0 (screening).
Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening).
LDL cholesterol >150 mg/dl.
Plasma triglycerides >400 mg/dl.
Contraindications to MRI (metallic implants, severe claustrophobia).
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.
Evidence of a secondary form of hypertension.
Initiation of new therapy with statins, ACEI/ARB, anti-oxidants, CCBs, diuretics, β blockers.
Type I diabetes mellitus
Known contraindication, including history of allergy to Spironolactone.
. Any surgical or medical condition which might alter pharmacokinetics of drug (e.g. renal transplant, liver failure, liver transplant).
Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
Significant hyponatremia defined as Na <130 meq/L.
History of prior malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer).
History of any severe, life-threatening disease.
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.
History of drug abuse within the last 2 years, noncompliance and unwillingness/inability to consent.
Pregnant women and nursing mothers.
Class III or IV Congestive Heart Failure.
Primary Hyperaldosteronism.

Sites / Locations

University Hospitals Cleveland Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Spironolactone

Placebo

Arm Description

Spironolactone

Placebo

Outcomes

Primary Outcome Measures

Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo

Secondary Outcome Measures

Left Ventricular Mass Index of Spironolactone vs. Placebo.

Myocardial Fibrosis (Change in Native T1) Spironolactone vs. Placebo

Change in 24-hour Ambulatory Systolic Blood Pressure of Spironolactone vs. Placebo

Measures of Insulin Resistance (HOMA-IR) of Spironolactone vs. Placebo

Full Information

NCT ID

NCT02169089

First Posted

June 18, 2014

Last Updated

July 10, 2023

Sponsor

University Hospitals Cleveland Medical Center

Collaborators

University of Maryland, University of Toronto, Winthrop University

1. Study Identification

Unique Protocol Identification Number

NCT02169089

Brief Title

Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

Official Title

Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

January 2016 (Actual)

Primary Completion Date

April 29, 2022 (Actual)

Study Completion Date

April 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospitals Cleveland Medical Center

Collaborators

University of Maryland, University of Toronto, Winthrop University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atherosclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

79 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Spironolactone

Arm Type

Experimental

Arm Description

Spironolactone

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Spironolactone

Other Intervention Name(s)

Aldactone

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo

Time Frame

56 weeks

Secondary Outcome Measure Information:

Title

Left Ventricular Mass Index of Spironolactone vs. Placebo.

Time Frame

56 weeks

Title

Myocardial Fibrosis (Change in Native T1) Spironolactone vs. Placebo

Time Frame

56 weeks

Title

Change in 24-hour Ambulatory Systolic Blood Pressure of Spironolactone vs. Placebo

Time Frame

11 weeks

Title

Measures of Insulin Resistance (HOMA-IR) of Spironolactone vs. Placebo

Time Frame

56 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

41 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. 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. Patients must be on ACE and/or ARB therapy with no planned dose adjustments. Exclusion Criteria: Uncontrolled hypertension (SBP>160 and/or DBP>95 mmHg at visit 0 (screening) and SBP >145 mm Hg at visit 2). GFR (MDRD) of <15 at Visit 0 (screening). Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening). LDL cholesterol >150 mg/dl. Plasma triglycerides >400 mg/dl. Contraindications to MRI (metallic implants, severe claustrophobia). 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. Evidence of a secondary form of hypertension. Initiation of new therapy with statins, ACEI/ARB, anti-oxidants, CCBs, diuretics, β blockers. Type I diabetes mellitus Known contraindication, including history of allergy to Spironolactone. . Any surgical or medical condition which might alter pharmacokinetics of drug (e.g. renal transplant, liver failure, liver transplant). Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. Significant hyponatremia defined as Na <130 meq/L. History of prior malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer). History of any severe, life-threatening disease. 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. History of drug abuse within the last 2 years, noncompliance and unwillingness/inability to consent. Pregnant women and nursing mothers. Class III or IV Congestive Heart Failure. Primary Hyperaldosteronism.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sanjay Rajagopalan

Organizational Affiliation

Chief, Cardiovascular Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospitals Cleveland Medical Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

12. IPD Sharing Statement

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Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

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