Effect of Dapagliflozin on Microvascular Function in Women With Symptoms of Coronary Artery Disease (SMILE)

A Single-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate Microvascular Disease After 12 Weeks of Therapy With Sodium-glucose Co-transporter 2 Inhibitor Compared to Placebo in Symptomatic Women With Non-obstructive Coronary Artery Disease

The goal of this clinical trial is to test the effects of a drug (in the drug class called sodium-glucose cotransporter 2 inhibitors) in women who have symptoms of ischemic heart disease. The main questions the study aims to answer are:

Does blood flow in the heart improve with study drug?

Participants will be randomly assigned to a 12-week course of the study drug, dapagliflozin 10mg, or placebo. Blood flow in the heart will be assessed using stress cardiac magnetic resonance imaging at baseline and 12 weeks. The researchers will compare the results from the two groups.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Ischemia
• Intervention / Treatment: Drug: Dapagliflozin 10mg Tab; Drug: Placebo

Detailed Description

This single-center clinical investigation is a randomized, double-blind, placebo controlled trial of dapagliflozin in women who have symptoms of myocardial ischemia but in whom obstructive coronary artery disease has been ruled out by testing within 2 years.

Aim: Determine whether dapagliflozin improves coronary blood flow in women.

Participants will be randomly assigned to a 12-week course of dapagliflozin 10mg oral or placebo. Participants will complete study assessments at baseline, 6 weeks of treatment, and 12 weeks of treatment. Peak myocardial blood flows at rest and with pharmacological stress will be assessed using cardiac magnetic resonance imaging at baseline and 12 weeks. Symptom surveys and lab work will be collected at baseline, 6 weeks, and 12 weeks of treatment. Participants will be closely monitored throughout study participation for adverse events. Results will be captured in a database and published in a peer-reviewed journal.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Caroline L Flournoy, PhD; Phone Number: 4349246104; Email: clf4w@uvahealth.org
• Study Contact Backup: Name: Nicole J Sprouse, RN; Phone Number: 434-982-1058; Email: njb6m@uvahealth.org

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
      • Principal Investigator: Patricia Rodrguez, MD
      • Contact: Caroline L Flournoy; Phone Number: 4349246104; Email: clf4w@uvahealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing to provide written informed consent.
• Signs and symptoms of suspected ischemia that prompted referral for further evaluation by cardiac catheterization or coronary computed tomography within two years of consent.
• No evidence of obstructive epicardial coronary artery disease (stenosis >50%) of a major epicardial vessel (>3mm) or a fractional flow reserve >0.80 by invasive catheterization or coronary computed tomography. (Participants who have not undergone cardiac catheterization or coronary angiogram within the last 2 years for their clinical care will be screened with computed angiogram of the coronary arteries to confirm eligibility).
• Estimated glomerular filtration rate ≥30ml/min/1.73m2 at enrollment
• For subjects having a history of type 2 diabetes mellitus: approval of diabetes care/prescribing provider

Exclusion Criteria:

• History of non-ischemic cardiomyopathy with left ventricular ejection fraction <40% or hypertrophic cardiomyopathy.
• History of congestive heart failure, severe pulmonary disease, liver disease
• History of Acute coronary syndrome within previous 30 days
• Stroke within the last 180 days or intracranial hemorrhage at any time.
• Severe Valvular disease
• Life expectancy <3 years, due to non-cardiovascular comorbidity.
• Pregnancy or women who are breast-feeding
• Type 1 diabetes mellitus
• History of diabetic ketoacidosis in subjects with Type 2 Diabetes Mellitus
• Symptomatic hypotension or systolic blood pressure <95 mmHg on 2 consecutive measurements
• Active malignancy requiring treatment at the time of visit
• Severe, unstable, or rapidly progressing renal disease at the time of randomization
• History of recurrent urinary tract, bladder, or kidney infections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin 10mg oral tablet.	Drug: Dapagliflozin 10mg Tab; Once daily oral dapagliflozin 10mg; Other Names: active drug
Placebo Comparator: Placebo; Placebo matching tablet.	Drug: Placebo; Placebo capsules formulated by pharmacy to be indistinguishable from active drug; Other Names: Placebo matching tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in myocardial perfusion reserve	Myocardial microvascular perfusion, defined as myocardial perfusion reserve as assessed by stress cardiac magnetic resonance imaging	Baseline and after 12 weeks of treatment

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Patricia Rodriguez-Lozano, MD, University of Virginia Health System

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2023
• Primary Completion (Actual): August 5, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Dapagliflozin
• Other Study ID Numbers: HSR220123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No