Microvascular Disease Exercise Trial (MOVE)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by University of Virginia
Sponsor:
Collaborators:
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
Jamieson Bourque, MD, University of Virginia
ClinicalTrials.gov Identifier:
NCT02045459
First received: January 17, 2014
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Coronary Microvascular Disease
Behavioral: Exercise Program
Drug: Medical Therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Assessment of Perfusion Reserve and Effects of Exercise in Microvascular Angina

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Change in MPR on CMR imaging from baseline with intensive medical therapy + supervised exercise versus intensive medical therapy alone. [ Time Frame: 20 weeks from first visit after consent is signed ] [ Designated as safety issue: Yes ]
    Determined with the use of a stress MRI after subject has been randomized and completed said randomized arm.


Secondary Outcome Measures:
  • Incremental change in MPR with exercise over intensive medical therapy alone in the exercise subgroup [ Time Frame: 20 weeks after randomization ] [ Designated as safety issue: Yes ]
    Determined by the use of stress MRI after subjects have completed their arm of randomization

  • Identification of reduced MPR (<2.0 ml/g/min) and borderline reduced MPR [ Time Frame: Within 30 days of screening visit ] [ Designated as safety issue: Yes ]
    This number is established by the use of a stress MRI


Estimated Enrollment: 165
Study Start Date: February 2014
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exercise Program and Medical Therapy
All subjects randomized to this arm will be given intensive medical therapy including - Isosorbide mononitrate, Lisinopril, Carvedilol, and Simvastatin. After 8 weeks of ONLY medication therapy, the subjects will begin a intensive exercise program. This will be supervised on site at UVA. Also, on days that the subject is not being supervised, they will be required to keep a journal of their exercise at home.
Behavioral: Exercise Program
Subject will be exercising on a treadmill 3x/week. Subjects progress will dictate increases/decreases in time of exercise and pace.
Drug: Medical Therapy
Subjects will be given medications listed above. They will be contacted periodically throughout the study to maximize effectiveness and to manage side effects if they occur.
Other Names:
  • Isosorbide mononitrate
  • Lisinopril
  • Carvedilol
  • Simvastatin
Active Comparator: Medical Therapy
All subjects randomized to this arm will be given intensive medical therapy including - Isosorbide mononitrate, Lisinopril, Carvedilol, and Simvastatin. They will NOT be in an exercise program. They will be called periodically to monitor effectiveness of medication and to see if any changes need to be made.
Drug: Medical Therapy
Subjects will be given medications listed above. They will be contacted periodically throughout the study to maximize effectiveness and to manage side effects if they occur.
Other Names:
  • Isosorbide mononitrate
  • Lisinopril
  • Carvedilol
  • Simvastatin

Detailed Description:

Cardiac angina is a major source of morbidity, affecting more than 5% of the U.S. population.2 It leads to more than 1.5 million hospitalizations and $190 billion in costs yearly.3 Obstructive coronary artery disease (CAD) is the most common cause of angina. However, no obstructive CAD is found on elective coronary angiography in more than 50% of cases.4, 5 These patients with angina but no obstructive CAD are a heterogeneous group. Some have noncardiac explanations for their angina or nonobstructive epicardial abnormalities such as coronary spasm. However, many patients with angina and no obstructive CAD have microvascular dysfunction from endothelial dysfunction or microvascular obstructive disease as the cause. These patients have microvascular angina.

The coronary microvasculature is responsible for more than 70% of coronary resistance and thus plays a key role in regulating blood flow to match demand.6 Microvascular dysfunction can occur in the setting of dilated, hypertrophic, and restrictive cardiomyopathies. However, it is commonly seen in the setting of atherosclerotic risk factors or can be idiopathic.6, 7 Microvascular dysfunction is manifest as insufficient stress myocardial blood flow and/or reduced myocardial perfusion reserve (MPR), the ratio of stress flow to rest flow, in response to a stress such as vasodilator administration. Absolute myocardial blood flow and MPR can be assessed noninvasively with high precision and accuracy by cardiac magnetic resonance (CMR) imaging Reduced MPR in patients with angina is associated with significant morbidity, including a high risk of cardiac events, high medical costs, and a decreased quality of life.Despite the poor prognosis of this population, therapeutic options to reduce angina and improve MPR have not been well studied. Preliminary analysis shows that statins may improve endothelial function. ACE-inhibitors and beta-blockers improve symptoms in Syndrome X, a related disorder in which patients have angina, no obstructive CAD, and ischemic changes but a better prognosis. Therapeutic exercise has also been used in the Syndrome X population, improving exercise tolerance and endothelial function and reducing symptom severity.Improvements in MPR could be expected with exercise due to the reduced resting flow and increased MPR seen in healthy volunteers and improved endothelial function from increased nitric oxide bioactivity in patients with probable microvascular dysfunction. However, no studies have examined the effect of these medications or their synergism with exercise on MPR, aerobic capacity, anginal symptoms, or quality of life in patients with angina and reduced MPR. Identification of an effective therapy that improved symptoms and prognosis would have dramatic impact on this highly prevalent patient population.

The primary goal of this study is to characterize which patients with angina but no obstructive CAD have reduced MPR and test the effectiveness of intensive medical therapy plus a 12-week supervised exercise program versus intensive medical therapy alone to improve MPR, aerobic capacity, and the patient-centered outcomes of cardiac events, angina severity, and quality of life in this population with microvascular angina.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, parapproteinemia 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 dypyridamole, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02045459

Contacts
Contact: Nicole J Sprouse, RN 434-982-1058 njb6m@virginia.edu

Locations
United States, Virginia
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22902
Contact: Jamieson Bourque, Medicine    434-982-1058    JMB8T@hscmail.mcc.virginia.edu   
Contact: Nicole J Sprouse, RN    434-982-1058    njb6m@virginia.edu   
Principal Investigator: Jamieson Bourque, MD, MHS         
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22901
Contact: Nicole J Sprouse, RN    434-982-1058      
Principal Investigator: Jamieson Bourque, MD         
Sponsors and Collaborators
University of Virginia
Astellas Pharma Global Development, Inc.
Investigators
Principal Investigator: Jamieson Bourque, BA,MD,MHS University of Virginia
  More Information

No publications provided

Responsible Party: Jamieson Bourque, MD, Assistant Professor, Cardiovascular Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT02045459     History of Changes
Other Study ID Numbers: 16821, 1K23HL119620-01
Study First Received: January 17, 2014
Last Updated: January 22, 2014
Health Authority: United States: Data and Safety Monitoring Board

Keywords provided by University of Virginia:
Microvascular Disease
Exercise
Angina
Chest pain

Additional relevant MeSH terms:
Simvastatin
Lisinopril
Carvedilol
Isosorbide Dinitrate
Isosorbide-5-mononitrate
Isosorbide
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Diuretics, Osmotic

ClinicalTrials.gov processed this record on September 29, 2014