aDAPt-ANOCA: Dapagliflozin for the Treatment of Angina With Non-Obstructive Coronary Artery Disease (ANOCA)

Phase 2Not Yet RecruitingNCT07741890

The Christ Hospital120 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

120

Conditions

Angina With Non-Obstructive Coronary Artery Disease Coronary Microvascular Dysfunction (CMD)

Interventions

Dapagliflozin (10mg Tab)DRUG

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.

Placebo ( FE)DRUG

Over encapsulated placebo to match active drug.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in quantitative myocardial perfusion reserve index (MPRI)

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.

Time frame: 180 days

Secondary Outcomes

Tissue Characterization by Cardiac MRI

Change in native T1 relaxation time (ms), T2 relaxation time (ms) to quantify diffuse and focal myocardial fibrosis, edema, and tissue composition.

Time frame: 180 days

Cardiac Structure and Function by Cardiac MRI

Change in left ventricular end-diastolic volume index (LVEDVi, mL/m²) and left ventricular end-systolic volume index (LVESVi, mL/m²).

Time frame: 180 days

Cardiac Strain by Cardiac MRI

Change in segmental strain parameters by calculating the global longitudinal strain (GLS, %), global circumferential strain (GCS, %), global radial strain (GRS, %).

Time frame: 180 Days

Epicardial Adipose Tissue (EAT) by Cardiac MRI

Total epicardial adipose tissue volume (mL) quantified from cardiac magnetic resonance imaging

Time frame: 180 Days

Oxygen-sensitive cardiac magnetic resonance (OS-CMR)-derived BMORE biomarkers

Quantitative myocardial oxygenation and regional oxygen-sensitive signal intensity changes measured by OS-CMR to assess myocardial oxygenation reserve and coronary vascular function.

Time frame: 180 days

Seattle Angina Questionnaire (SAQ)

Central Contacts

Assistant Director, Regulatory and Compliance, MS

CONTACT

15135851777 lindner_regulatory@thechristhospital.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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.

Time frame: Baseline, 90 days, 180 days and 30 days after stopping treatment

6 minute walk test

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.

Time frame: Baseline, 90 days, 180 days and post-drug assessment

Change in Bloodwork and Biomarkers Endothelial Dysfunction and Inflammation

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.

Time frame: Baseline, 90 days, 180 days and 30 days after stopping treatment.

Change in Extracellular Volume Fraction (ECV) by Cardiac MRI

Change in extracellular volume fraction (ECV, %) measured by cardiovascular magnetic resonance (CMR) to quantify diffuse myocardial fibrosis and alterations in myocardial tissue composition.

Time frame: 180 days

Cardiac Structure and Function by Cardiac MRI

Change in left ventricular mass index (LVMi, g/m²).

Time frame: 180 days

Cardiac Structure and Function by Cardiac MRI

Change in relative wall thickness (RWT).

Time frame: 180 days

Cardiac Structure and Function by Cardiac MRI

Change in left left ventricular ejection fraction (LVEF, %).

Time frame: 180 days

Cardiac Structure and Function by Cardiac MRI

Change in estimated left ventricular filling pressures (E/e' ratio).

Time frame: 180 days

Cardiac Strain by Cardiac MRI

Change in filling pressures (E/e' ratio).

Time frame: 180 days

Duke Activity Status Index (DASI)

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.

Time frame: Baseline, 90 days, 180 days and 30 days after stopping treatment

International Physical Activity Questionnaire (IPAQ)

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.

Time frame: Baseline, 90 days, 180 days and 30 days after stopping treatment

The University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOB)

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.

Time frame: Baseline, 90 days, 180 days and 30 days after stopping treatment

Short Form-36 Health Survey (SF-36)

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.

Time frame: Baseline, 90 days, 180 days and 30 days after stopping treatment

Change in Late Gadolinium Enhancement (LGE) by Cardiac MRI

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.

Time frame: 180 days