Microvascular Disease Exercise Trial

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 165
• Participant gender: Both

Summary

For part of this study, we are collecting information from patients that have been experiencing the symptoms mentioned above. We are taking this information and creating a chest pain registry to follow trends and compare different patients having similar symptoms. We hope to gain insight into the quality of life, symptoms, and cardiac events of those who are having similar symptoms. The type of information we will collect includes: demographics, quality of life, levels of anxiety related to angina pain and cardiac events occurring within a 2 year period of time.

In addition, we are performing a cardiac stress MRI for research purposes to look at the blood flow in the small vessels in your heart. During the stress cardiac MRI, we will give you a medication called Regadenoson (Lexiscan) which "stresses" your heart by dilating the blood vessels to your heart. This drug is approved by the U.S. Food and Drug Administration (FDA) for this purpose. We will then be able to measure the myocardial perfusion reserve (MPR) which is a measure of blood flow through the small blood vessels to see if an abnormal MPR and small blood vessel disease is associated with an increased risk of cardiovascular events, such as heart attack. At this point, there is no specific therapy for small vessel disease. In addition we have phase II of this study which is to determine if exercise and intensive medical therapy together compared to intensive medical therapy alone improves pain from the heart and improves overall quality of life.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Virginia
• Collaborators: Astellas Pharma Global Development, Inc.; National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Carvedilol; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate; Lisinopril; Simvastatin
• Last Updated: 2016-05-24

Criteria

Inclusion Criteria:

• Age 18 - 85

• Anginal symptoms of chest pain, dyspnea on exertion, or other anginal equivalent suspected to be secondary to myocardial ischemia

• Coronary angiogram without obstructive epicardial coronary artery disease (≥50% epicardial stenosis or fractional flow reserve of <0.80) within 6 months prior to enrollment or date of CMR #1, whichever is later and without intervening signs or symptoms suggestive of new obstructive epicardial CAD.

Exclusion Criteria:

• Prior CABG (due to limitations of CMR quantitative perfusion in this population)

• Prior myocardial infarction (due to its effects on myocardial flow reserve)

• Hypertrophic or restrictive cardiomyopathy

• Coronary vasospasm

• Acute coronary syndrome unless concurrent coronary angiography reveals no epicardial stenoses of >50%

• Contraindications to CMR including - intracranial aneurysm clips, implantable pacemaker or defibrillator, metal cochlear/intraocular implants, any metallic implant not listed as magnetic resonance compatible, severe claustrophobia or other inability to tolerate a 30 minute CMR study

• GFR < 45 ml/min/1.73² (to avoid nephrogenic systemic fibrosis and iodinated contrast dye - mediated ATN) based on creatinine within 30 days of CMR #1

• Acute kidney injury, defined by the KDIGO Clinical Practice Guidelines as an increase in serum creatinine of ≥0.3 mg/dL within 48 hours, an increase in serum creatinine ≥1.5 times baseline thought to have occurred in the past 7 days, or a urine volume <0.5mL/kg/h for 6 hours

• Severe liver disease, paraproteinemia syndromes (such as multiple myeloma), hepatorenal syndrome, or planned liver transplantation (gadolinium contraindication)

• Pregnancy (assessed by serum beta- HCG prior to CMR) due to unclear gadolinium fetal effects

• Known hypersensitivity to regadenoson, or gadolinium

• Other contraindications to regadenoson (heart rate < 40 bpm, 2nd or 3rd degree heart block, sick sinus syndrome without a pacemaker, severe asthma or COPD with ongoing wheezing or hospitalization within the past 6 months, systolic blood pressure <90mmHg, recent use of dipyridamole, methylxanthine (such as aminophylline) or dipyridamole use within the past 48 hours, or caffeine within 12 hours)

• Atrial fibrillation with rapid ventricular response, frequent ectopy, or other contraindications to ECG gating

• Inability to provide informed consent

• Life expectancy of < 2 years

3. List any restrictions on use of other drugs or treatments.

• Subject will be asked to refrain from use of caffeine for 12 hours and methylxanthines and dipyridamole for 48 hours prior to any administration of regadenoson. Subject may not participate if pregnant or breastfeeding.

Phase 2:

1. List the criteria for inclusion

• Enrollment in phase #1.

• MPR <2.0 ml/g/min on CMR #1.

2. List the criteria for exclusion

•Unable to exercise.

3. List any restrictions on use of other drugs or treatments. Subject will be asked to refrain from use of caffeine for 12 hours and methylxanthines and dipyridamole for 48 hours prior to any administration of regadenoson. Subject may not participate if pregnant or breastfeeding.