Coronary Microvascular DiseaseMOVENCT02045459
Microvascular Disease Exercise Trial
A study testing Exercise Program in people with Coronary Microvascular Disease, run by University of Virginia at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Coronary Microvascular Disease
- What is being tested?
- Exercise Program
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2014to 17 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 24Show fewer
- 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:
- List the criteria for inclusion
- Enrollment in phase #1.
- MPR <2.0 ml/g/min on CMR #1.
- List the criteria for exclusion
- •Unable to exercise.
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Virginia
Charlottesville, Virginia, 22901
University of Virginia
Charlottesville, Virginia, 22902
About this study
Official title: Assessment of Perfusion Reserve and Effects of Exercise in Microvascular Angina
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.
Read the 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.
- Conditions
- Coronary Microvascular Disease
- Being tested
- Exercise Program
- Keywords
- Microvascular Disease, Exercise, Angina, Chest pain
- Medical subject headings
- Microvascular Angina, Motor Activity, Angina Pectoris, Chest Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise ProgramBehavioural
Subject will be exercising on a treadmill 3x/week. Subjects progress will dictate increases/decreases in time of exercise and pace.
| Study group | Role | What they receive |
|---|---|---|
| Exercise Program and Medical Therapy | Experimental | 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. Receives: Behavioral: Exercise Program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in MPR on CMR imaging from baseline with intensive medical therapy + supervised exercise versus intensive medical therapy alone.
Determined with the use of a stress MRI after subject has been randomized and completed said randomized arm.
Measured: 20 weeks from first visit after consent is signed
Secondary outcomes (2)
Incremental change in MPR with exercise over intensive medical therapy alone in the exercise subgroup
Determined by the use of stress MRI after subjects have completed their arm of randomization
Measured: 20 weeks after randomization
Identification of reduced MPR (<2.0 ml/g/min) and borderline reduced MPR
This number is established by the use of a stress MRI
Measured: Within 30 days of screening visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2014 (estimated)
- Study startMay 2014
- Primary completion21 Jan 2020
- Study completion17 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Microvascular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Global Development, Inc., National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Jamieson Bourque, MD, University of Virginia
- Investigators
- Jamieson Bourque, BA,MD,MHS, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02045459
- Sponsor's protocol ID
- 16821
- Other IDs
- 1K23HL119620-01
- Acronym
- MOVE
- Status last verified
- May 2021
- First submitted
- 17 Jan 2014
- Last updated
- 19 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Perfusion Reserve and Effects of Exercise in Microvascular Angina
- ClinicalTrials.gov ID
- NCT02045459
- Acronym / sponsor ID
- MOVE / 16821
- Conditions
- Coronary Microvascular Disease
- Keywords
- Microvascular Disease, Exercise, Angina, Chest pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Astellas Pharma Global Development, Inc., National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- May 2014
- Primary completion
- 21 Jan 2020 (actual)
- Study completion
- 17 May 2021 (actual)
- First posted
- 24 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Exercise Program and Medical Therapy | Experimental | Behavioral: Exercise ProgramAll 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (24 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise ProgramSubject will be exercising on a treadmill 3x/week. Subjects progress will dictate increases/decreases in time of exercise and pace. | Behavioural | Exercise Program and Medical Therapy |
Primary outcome
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
Determined with the use of a stress MRI after subject has been randomized and completed said randomized arm.
2 secondary outcomes
Incremental change in MPR with exercise over intensive medical therapy alone in the exercise subgroup
Time frame: 20 weeks after randomization
Identification of reduced MPR (<2.0 ml/g/min) and borderline reduced MPR
Time frame: Within 30 days of screening visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jamieson Bourque, BA,MD,MHS principal investigator
University of Virginia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise Program in people with Coronary Microvascular Disease, run by University of Virginia at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2021.