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

Sponsor

University of Virginia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05762952

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Ischemia	Drug: Dapagliflozin 10mg Tab Drug: Placebo	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Pharmacy will manage the randomization of study participants. Assignments will not be unmasked until all outcomes have been assessed.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in myocardial perfusion reserve [Baseline and after 12 weeks of treatment]
Myocardial microvascular perfusion, defined as myocardial perfusion reserve as assessed by stress cardiac magnetic resonance imaging

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Virginia

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Patricia Rodriguez Lozano, Assistant Professor of Medicine, University of Virginia

ClinicalTrials.gov Identifier:

NCT05762952

Other Study ID Numbers:

HSR220123

First Posted:

Mar 10, 2023

Last Update Posted:

Mar 10, 2023

Last Verified:

Feb 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Coronary Artery Disease

Study Results

No Results Posted as of Mar 10, 2023