NCT02169089

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
79

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jan 2016

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 18, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 20, 2014

Completed
1.5 years until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 29, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 29, 2022

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

August 1, 2023

Completed
Last Updated

August 1, 2023

Status Verified

July 1, 2023

Enrollment Period

6.3 years

First QC Date

June 18, 2014

Results QC Date

May 22, 2023

Last Update Submit

July 10, 2023

Conditions

Atherosclerosis

Outcome Measures

Primary Outcomes (1)

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

    56 weeks

Secondary Outcomes (4)

  • Left Ventricular Mass Index of Spironolactone vs. Placebo.

    56 weeks

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

    56 weeks

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

    11 weeks

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

    56 weeks

Study Arms (2)

Spironolactone

EXPERIMENTAL

Spironolactone

Drug: Spironolactone

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

SpironolactoneDRUG

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.

Also known as: Aldactone
Spironolactone
PlaceboDRUG

Placebo

Placebo

Eligibility Criteria

Age41 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

  • Rajagopalan S, Dobre M, Dazard JE, Vergara-Martel A, Connelly K, Farkouh ME, Gaztanaga J, Conger H, Dever A, Razavi-Nematollahi L, Fares A, Pereira G, Edwards-Glenn J, Cameron M, Cameron C, Al-Kindi S, Brook RD, Pitt B, Weir M. Mineralocorticoid Receptor Antagonism Prevents Aortic Plaque Progression and Reduces Left Ventricular Mass and Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease: The MAGMA Trial. Circulation. 2024 Aug 27;150(9):663-676. doi: 10.1161/CIRCULATIONAHA.123.067620. Epub 2024 Aug 12.

    PMID: 39129649DERIVED

MeSH Terms

Conditions

Atherosclerosis

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Results Point of Contact

Title
Dr. Sanjay Rajagopalan
Organization
University Hospitals Cleveland Medical Center
Sanjay.Rajagopalan@uhhospitals.org
216-844-5191

Study Officials

  • Sanjay Rajagopalan

    Chief, Cardiovascular Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief, Cardiovascular Medicine

Study Record Dates

First Submitted

June 18, 2014

First Posted

June 20, 2014

Study Start

January 1, 2016

Primary Completion

April 29, 2022

Study Completion

April 29, 2022

Last Updated

August 1, 2023

Results First Posted

August 1, 2023

Record last verified: 2023-07

Locations

US(1)