Angina With Non-Obstructive Coronary Artery Disease, Coronary Microvascular Dysfunction (CMD)
Conditions
Brief summary
The primary purpose of this study is to evaluate the efficacy of DAPA for the treatment of coronary microvascular dysfunction (CMD) among patients with angina and no obstructive coronary artery disease (ANOCA) and established CMD as compared to placebo.
Interventions
The study will be double blinded by over encapsulation of Dapagliflozin with a matching lactose powder capsule used for the placebo group. All enrolled participants who meet inclusion / exclusion will receive either 10 mg Dapagliflozin (10mg) for 180 days, or placebo, randomized 1:1.
DRUGPlacebo ( FE)
Over encapsulated placebo to match active drug.
Sponsors
The Christ Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is older than 18 years of age * Participant is willing and able to sign informed consent * Participant is willing to comply with the specified follow-up evaluations * Anginal Symptoms (chest pain, pressure, dyspnea on exertion, or anginal equivalents * Stable CMD treatment (ie: Guideline Directed Medical Treatment) for \>30 days prior to enrollment with no plans to change treatment during trial duration * Non-obstructive CAD: Patients with non-obstructive CAD (coronary narrowing of \<50%, and/or FFR ≥0.80) assessed by Left Heart Cath or CCTA within the past 5 years * Diagnosis of CMD based on prior testing within 5 years: 1. Invasive Coronary Functional Testing derived Coronary Flow Reserve (CFR) \< 2.5 2. Stress Cardiac MRI measure myocardial perfusion reserve index (MPRI) \<2.5 3. Stress Positron Emission Tomography (PET) measured Myocardial Blood Flow \<2.5
Exclusion criteria
* Clinical Diagnosis Type 1 or 2 diabetes on medical treatment * Clinical Diagnosis of Heart failure with preserved ejection fraction (HFpEF) * Symptomatic Postural Orthostatic Tachycardia Syndrome (POTS) * History of coronary artery bypass graft (CABG) * Severe valvular heart disease (any valve) * BMI \> 35 kg/m² * Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), hypertrophic obstructive cardiomyopathy or known pericardial constriction * Current treatment with any SGLT-2 inhibitor * Hypersensitivity to SGLT2i * Impaired renal function (eGFR less than 30 mL/min/1.73 m2) * Symptomatic hypotension * History of genital mycotic infections * History of chronic urinary tract infections (UTIs) * Pre-menopausal women (last menstruation ≤ 1 year prior to informed consent) who: - are nursing or pregnant or - are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if allowed by local Authorities), double barrier method and vasectomized partner. * Contraindications to CMRI such as ferromagnetic implants and materials, Cochlear implants, implanted neurostimulators, severe obesity, and certain cerebral aneurysm clips, severe claustrophobia. * Comorbidities limiting life expectancy to less than one year * Any clinical condition that might interfere with the trial protocol or the Participant's ability to be compliant with the trial protocol (e.g., active alcohol or drug abuse, dementia). * Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s). Patients participating in a purely observational trial will not be excluded * Any other condition which, in the opinion of the investigator, may preclude the participant from safe participation in the study or compromise data integrity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in quantitative myocardial perfusion reserve index (MPRI) | 180 days | Change from baseline in the dapagliflozin group compared with the placebo group. A normal MPRI value is usually above 2.0. A value below 1.5 often points to reduced blood flow or poor heart function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tissue Characterization by Cardiac MRI | 180 days | Change in native T1 relaxation time (ms), T2 relaxation time (ms) to quantify diffuse and focal myocardial fibrosis, edema, and tissue composition. |
| Cardiac Structure and Function by Cardiac MRI | 180 days | Change in left ventricular end-diastolic volume index (LVEDVi, mL/m²) and left ventricular end-systolic volume index (LVESVi, mL/m²). |
| Cardiac Strain by Cardiac MRI | 180 Days | Change in segmental strain parameters by calculating the global longitudinal strain (GLS, %), global circumferential strain (GCS, %), global radial strain (GRS, %). |
| Epicardial Adipose Tissue (EAT) by Cardiac MRI | 180 Days | Total epicardial adipose tissue volume (mL) quantified from cardiac magnetic resonance imaging |
| Oxygen-sensitive cardiac magnetic resonance (OS-CMR)-derived BMORE biomarkers | 180 days | Quantitative myocardial oxygenation and regional oxygen-sensitive signal intensity changes measured by OS-CMR to assess myocardial oxygenation reserve and coronary vascular function. |
| Seattle Angina Questionnaire (SAQ) | Baseline, 90 days, 180 days and 30 days after stopping treatment | The Seattle Angina Questionnaire (SAQ) is a validated, disease-specific instrument designed to measure the impact of angina on patients' health status and quality of life. The questionnaire assesses five domains: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease-specific quality of life. Scores range from 0 to 100, with higher scores indicating better health status and fewer angina-related limitations. |
| 6 minute walk test | Baseline, 90 days, 180 days and post-drug assessment | Change in total distance walked in 6 minutes (meters), along with pre- and post-test measurements of oxygen saturation (SpO₂), heart rate, perceived exertion (Borg Rating of Perceived Exertion), and symptoms (e.g., dyspnea and fatigue). All parameters are combined to measure functional capacity. |
| Change in Bloodwork and Biomarkers Endothelial Dysfunction and Inflammation | Baseline, 90 days, 180 days and 30 days after stopping treatment. | Change in CBC, HbA1c, insulin resistance measures, iron studies, lipid profile, serum ketones, EPO levels, and NT-proBNP concentrations measured to evaluate systemic inflammation, endothelial dysfunction, metabolic health, and cardiovascular status. |
| Change in Extracellular Volume Fraction (ECV) by Cardiac MRI | 180 days | Change in extracellular volume fraction (ECV, %) measured by cardiovascular magnetic resonance (CMR) to quantify diffuse myocardial fibrosis and alterations in myocardial tissue composition. |
| Duke Activity Status Index (DASI) | Baseline, 90 days, 180 days and 30 days after stopping treatment | The Duke Activity Status Index (DASI) is a validated 12-item self-administered questionnaire that evaluates functional capacity by assessing a participant's ability to perform common activities of daily living requiring varying levels of physical exertion. Responses are used to calculate a weighted score that correlates with peak oxygen uptake (VO₂ peak) and functional exercise capacity. The DASI provides a practical estimate of cardiovascular functional status and has been extensively validated in patients with ischemic heart disease and heart failure. Scores range from 0 to 58.2, with higher scores indicated improved function. |
| International Physical Activity Questionnaire (IPAQ) | Baseline, 90 days, 180 days and 30 days after stopping treatment | The International Physical Activity Questionnaire (IPAQ) is a standardized, validated instrument used to quantify habitual physical activity over the previous seven days. The questionnaire assesses the frequency and duration of walking, moderate-intensity activity, vigorous-intensity activity, and sedentary behavior across work, transportation, household, and leisure domains. IPAQ results will be used to characterize participants' baseline activity levels and evaluate changes in physical activity during the intervention period. Scores are calculated as weekly metabolic equivalents beginning with 0 to 3000+ METs with higher METS indicating increased physical activity. |
| The University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOB) | Baseline, 90 days, 180 days and 30 days after stopping treatment | UCSD-SOB is a validated patient-reported outcome measure designed to quantify dyspnea during activities of daily living. The questionnaire evaluates the severity of shortness of breath across a broad range of physical activities and includes items assessing limitations due to breathlessness. Scores range from 0 to 120 with higher scores indicating worse dyspnea. |
| Short Form-36 Health Survey (SF-36) | Baseline, 90 days, 180 days and 30 days after stopping treatment | The 36-Item Short Form Health Survey (SF-36) is a widely validated generic measure of health-related quality of life. The questionnaire evaluates eight health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional health, and mental health. Domain scores are summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, providing a comprehensive assessment of overall health status. The SF-36 is designed to detect changes in both physical and psychosocial well-being over time and allows comparison with other disease populations and the general population. Scores on the SF-36 range from 0 to 100 with increased scores representing better health in that domain. |
| Change in Late Gadolinium Enhancement (LGE) by Cardiac MRI | 180 days | Change in late gadolinium enhancement (LGE, % of left ventricular mass) measured by cardiovascular magnetic resonance (CMR) to quantify focal myocardial fibrosis and myocardial scar burden. |
Contacts
CONTACTAssistant Director, Regulatory and Compliance, MS
Outcome results
None listed