Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03876223
Other study ID # 54999
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date July 24, 2019
Est. completion date February 28, 2025

Study information

Verified date February 2024
Source Cedars-Sinai Medical Center
Contact Nicole Tovar
Phone 310-248-6960
Email nicole.tovar@cshs.org
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The purpose of this study is to examine small vessel disease (a condition in which the small arteries in the heart become narrowed). The investigators want to know how the small vessel disease contributes to pre-HFpEF (a condition with inadequate heart muscle function in the setting of preserved muscle pumping) and to better identify potential treatment for prevention of HFpEF. The main procedures of this study include up to 2 clinic visits (initial visit and a second clinical visit only if participants are unable to complete all research procedures at the initial visit); a 6-week phone interview visit, 4 quarterly follow-up phone interview visits in year 1; year 1 follow up cardiac MRI based on availability and ongoing annual follow-up phone interview visits to track progress. If participants choose to take part in this study, participants direct participation will end after 1 year, participants will then have the option of participating in ongoing annual check-in calls. Participants will be asked to undergo a physical exam and provide a completed medical history; complete a Cardiovascular (or Cardiac) Magnetic Resonance Imaging (CMRI) with contrast agent; complete questionnaires to describe heart symptoms and overall quality of life status; undergo blood draws to provide blood samples for research testing, and allow the study team to have access to medical records.


Description:

Coronary microvascular dysfunction (CMD) due to changes in the function and structure of coronary microcirculation in the absence of obstructive coronary artery disease (CAD) is poorly understood. Ischemia with no obstructive CAD (INOCA) and myocardial infarction with no obstructive CAD (MINOCA) are increasingly observed in women and men. Once established, the investigators will be well positioned to aggressively target identified mechanistic targets in a specific well-characterized at-risk population, with the primary goal of preventing progression to HFpEF. To address this novel hypothesis, the investigators propose the following Specific Aims: Aim 1: Test the hypothesis that CMD-related ischemia contributes to myocellular damage and impaired ventricular relaxation. CMD will be measured directly, using our established intracoronary pharmacological vasoactive protocol, in subjects with signs/symptoms of ischemia but no obstructive CAD. In our labs (>420 patients), ~60% of those tested have evidence for CMD. All subjects will perform provocative stress testing with isometric handgrip - chosen for its unique ability to increase myocardial afterload and myocardial oxygen demand - while myocardial ischemia will be assessed directly through invasive simultaneous arterial and coronary sinus/great cardiac vein oxygen tension and lactate measurements, and continuous ECG's recordings. Left ventricular function will be directly assessed using Millar-catheter LV pressure-volume loops (perfected in our lab over the past 24 months). Stress-induced myocellular damage will be directly measured by coronary sinus/great cardiac vein hs-cTnI. Aim 2: Test the hypothesis that CMD-related ischemic myocellular damage contributes to LV diastolic dysfunction progression. Subjects from Aim 1 will also undergo comprehensive cardiac magnetic resonance imaging (CMRI) at enrollment and 1-2 years later. The investigators will evaluate CMRI LV perfusion, myocardial scar, diffuse fibrosis, LV remodeling, and diastolic function. The investigatorswill leverage the strengths and resources of our world-renowned proteomics core to establish evidence of chronic myocellular damage using prospectively repeated ambulatory hs-cTnI determinations.


Recruitment information / eligibility

Status Recruiting
Enrollment 180
Est. completion date February 28, 2025
Est. primary completion date February 28, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion: 1. 180 symptomatic men and women undergoing invasive coronary angiography for suspected ischemia with no obstructive CAD, defined as =50% luminal diameter stenosis in =1 epicardial coronary artery. 2. Preserved left ventricular ejection fraction (EF) =45% 3. Be > 18 years old 4. Be able to meet the requirement for a cardiac MRI, which means no metal devices in your chest, no claustrophobia and no angioedema 5. Be competent to give informed consent Exclusion: 1. Subjects with severe or chronic kidney disease (CKD) with GFR<405 or acute kidney injury 2. Subjects with allergy to animal dander will be excluded since imaging will be done in BIRI (BIRI scanners are also used to image animals). 3. Subjects who have had four or more prior previous gadolinium contrast scans 4. Allergy/ hypersensitivity to adenosine, gadolinium, aminophylline or regadenoson 5. Second- or third-degree A-V block 6. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker) 7. Subjects with mild to severe asthma

Study Design


Related Conditions & MeSH terms

  • Coronary Microvascular Dysfunction
  • Heart Failure
  • Heart Failure With Preserved Ejection Fraction (HFpEF)
  • Ischemia

Locations

Country Name City State
United States University of Florida Gainesville Florida
United States Cedars-Sinai Medical Center Los Angeles California

Sponsors (2)

Lead Sponsor Collaborator
Cedars-Sinai Medical Center University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary CMR imaging Change from Baseline at 1 year follow up will be assessed. Baseline, Annual follow up
Primary Rest-stress Millar pressure-volume measurement LV diastolic function will be measured using LV end-diastolic pressure, minimal rate of LV pressure change (dP/dtmin). Baseline
Secondary Questionnaire Symptom History Questionnaire. Change from Baseline at each visit will be measure. There is no scale ranges for this questionnaire. This questionnaire results in raw data that is not calculated into a score or scale. Baseline, 6 week, quarterly(year 1) and annual follow up
Secondary Questionnaire WISE Symptoms History Detailed information on chest pain symptoms will include the WISE female angina questionnaire.
Change from Baseline at each visit will be measure. There is no scale ranges for this questionnaire. This questionnaire results in raw data that is not calculated into a score or scale.
Baseline, quarterly(year 1) and annual follow up
Secondary SEATTLE ANGINA QUESTIONNAIRE The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life.
Each scale is transformed to a score of 0 to 100. A higher score means better control of chest pain, chest tightness, angina, or shortness of breath.
Change from Baseline at each visits will be measure.
Baseline, 6 week and annual follow up
Secondary Duke Activity Status Inventory (DASI) It is a self-administered questionnaire that measures a patient's functional capacity.
Change from Baseline at each visit will be measure. Maximum response is a total of 16.7 while minimum is 0.
Baseline, 6 week and annual follow up
See also
  Status Clinical Trial Phase
Completed NCT06306066 - Coronary Thermo-dilution Derived Flow-indices in Chronic Coronary Syndrome
Recruiting NCT05288361 - The DISCOVER INOCA Prospective Multi-center Registry
Terminated NCT04614467 - A Placebo-Controlled Trial of CLBS16 in Subjects With Coronary Microvascular Dysfunction Phase 2
Recruiting NCT06089031 - Belgian Registry on Coronary Function Testing
Enrolling by invitation NCT06083155 - The NetherLands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT)
Completed NCT05009667 - A Prospective, Multi-center Clinical Trial for Evaluating the Effectiveness and Safety of Online Coronary Angiography-Derived Index of Microcirculatory Resistance (caIMR)
Active, not recruiting NCT05197361 - Microvascular Coronary Resistance and Absolute Coronary FLOW in Patients With Percutaneous Intervention of a Chronic Total Occlusion
Not yet recruiting NCT06332131 - Effects of Immune Checkpoint Inhibitors on Coronary Microvasculature
Recruiting NCT05825339 - Absolute Flow for Ischemia With No Obstructive Coronary Arteries
Recruiting NCT05294887 - Randomized Trial to Examine a Differential Therapeutic Response in Symptomatic Patients With Non-obstructive Coronary Artery Disease Phase 4
Not yet recruiting NCT05790876 - Super Saturated Oxygen (SSO2) Therapy in Patients With ST-segment Elevation Myocardial Infarction (STEMI) and Action on Coronary Microcirculation Dysfunction N/A
Completed NCT04959357 - The Evaluation of Left Ventricular Systolic Function in Different Types of Ischemic Heart Disease
Recruiting NCT06393478 - Southeastern Europe Microcirculation Registry
Completed NCT04523168 - Feasibility and Efficacy of Coronary Sinus Narrowing in Patients With Coronary Microvascular Dysfunction N/A
Recruiting NCT05711719 - Vericiguat in Patients With Metabolic Syndrome and Coronary Vascular Dysfunction Phase 2
Recruiting NCT06294730 - COronary Microcirculation and Troponin Elevation in Septic Shock
Recruiting NCT05841485 - COVID-19 Microvascular Evaluation Trial
Completed NCT05471739 - Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler
Completed NCT02333591 - Effect of Intact GLP-1 (7-36) and GLP-1 Metabolite (9-36) on Coronary and Peripheral Vascular Function in Adults Phase 4
Completed NCT01014949 - Microcirculation Assessment in Diabetes and Metabolic Syndrome N/A