Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01655043
Recruitment Status : Completed
First Posted : August 1, 2012
Results First Posted : March 27, 2015
Last Update Posted : April 20, 2015
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
James Carr, Northwestern University

Brief Summary:

Coronary artery disease (CAD, coronary heart disease) is the leading cause of death in the U.S., causing 1 in 5 deaths in 2005. The current method for diagnosing coronary artery disease that is considered most accurate is coronary angiography however it involves risk and radiation. Alternatively nuclear imaging test and MRI stress test only permits the semi qualitative analysis of the myocardial perfusion images.

In this proposal the investigators will develop a means to calculate Coronary Flow Reserve (CFR) using the MRI. the investigators approach has the potential to reduce mortality from myocardial infarction by effecting a change in the patient management paradigm. Absolute quantification of myocardial perfusion will detect coronary stenosis and CAD in patients with more accuracy than the semi-quantitative or qualitative analysis of perfusion images. Measurement of Coronary Flow Reserve is important for the following reasons: decrease of coronary flow reserve has been identified as a first effect of CAD; it provides an objective measure of treatment efficacy.

The purpose of this study is to compare images from nuclear stress test and/or coronary angiography with Magnetic Resonance Imaging (MRI) that will evaluate subjects with coronary artery disease calculating myocardial blood flow using a novel MRI technique combined to an extracellular Gadolinium-based contrast agent and stressor agent

Condition or disease Intervention/treatment Phase
Myocardial Ischemia Drug: Regadenoson Drug: gadofoveset trisodium Phase 2

Detailed Description:

The main hypothesis the investigators will test is that changes in myocardial blood volume, under physiologic stress, correlate with myocardial flow reserve as measured in low spatial resolution nuclear SPECT scans. Secondary hypothesis is that stress perfusion as quantified with bolus height corrected gadofosveset trisodium images, better correlate with SPECT perfusion than uncorrected, relative perfusion values.

The investigators propose implementing the scan protocol using a 1.5T or 3.0T MRI scanner. The investigators will scan a series of 20 patients recruited from the nuclear stress lab at Northwestern Memorial Hospital. These subjects will be approached and enrolled into a HIPPA Compliant, IRB approved research study to assess the effectiveness of myocardial perfusion and blood volume images to measure myocardial blood volume. Subjects will be scanned with a modified version of the clinical stress-perfusion protocol. Correlation analysis will be used to test the hypothesis that quantitative blood volume is an indicator of myocardial flow reserve.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI
Study Start Date : September 2012
Actual Primary Completion Date : February 2014
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Regadenoson
U.S. FDA Resources

Arm Intervention/treatment
Experimental: coronary artery disease patients
Patients with suspected coronary artery disease prospectively recruited for myocardial perfusion MRI. All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar, Lantheus) at both stress and rest. Stress to be induced using 5 ml intravenous (IV) regadenoson (Lexiscan, Astellas US LLC), and the effects of regadenoson were reversed with 50 mg IV aminophylline following the completion of stress imaging.
Drug: Regadenoson
Regadenoson will be infused intravenously 0.4 mg/5 mL (0.08 mg/mL) as a single bolus.
Other Name: Lexiscan
Drug: gadofoveset trisodium
All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar) at both stress and rest.
Other Name: Ablavar

Primary Outcome Measures :
  1. Quantification of Myocardial Blood Volume [ Time Frame: outcome measured following single MRI scan ]
    The investigators anticipated that a novel MRI imaging protocol using a high relaxivity blood-pool contrast agent (gadofosveset trisodium) would be capable of quantifying coronary flow reserve based on quantification of myocardial blood volume and would be correlated with myocardial flow reserve as measured in low spatial resolution nuclear SPECT scans. Pre- and post- gadofosveset trisodium images were to be used to calculate the myocardial blood volume. Myocardial blood volume is derived from an equation of the relaxation times of hydrogen atoms in the blood and myocardium. If the agent administered did not behave as a true intravascular agent in the myocardium, quantification of myocardial intravascular blood volume (and hence a calculated coronary flow reserve) could not be calculated using the specified approach. In this case, relaxation times would be reported. Relaxation (R) times are measured in inverse seconds.

Secondary Outcome Measures :
  1. Coronary Blood Volume Calculation Using MRI Stress Perfusion [ Time Frame: 18 months ]
    The investigators anticipate that CBV changes (in ml/100g of tissue) under stress reflect complementary physiologic feed back to stress perfusion scans, contrary to the hypothesis by many groups who claim that cardiac BOLD and/or rest-perfusion scans can determine without recourse to exercise or pharmacological stress.

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 89 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Under an Institutional Committee on Human Research board approved protocol, 20 patients with a suspected myocardial ischemic disease with positive stress nuclear medicine test laboratory will be recruited in this prospective study. All subjects will be screened for GFR within 24 hours before the exam. All patients must have a GFR > 30 mL/min/1.73m2 to be included in the study.

All subjects will be selected following the Nephrogenic Systemic Fibrosis (NSF) guidelines. All dialysis patients or end-stage renal disease patients with a creatinine clearance of < 30mL/min will not be selected for the study to avoid NSF.

Exclusion Criteria:

  1. Age 18 to 89 years;
  2. Known contraindication to MR imaging (such as pacemaker placement, magnetic implants, etc);
  3. Claustrophobia;
  4. Inability to perform an adequate breath-hold for imaging,
  5. Inability to provide informed consent;
  6. all subjects will be will be screened for GFR within 24 hours before the exam and subjects presenting with GFR < 60 ml/min will be excluded;
  7. Pregnant and lactating women;
  8. Patients with hypersensitivity to gadolinium contrast agents, metoprolol, adenosine, or nitroglycerin;

10) Contra indication for Regadenoson

  1. 2nd- or 3rd-degree AV block (except in patients with a functioning artificial pacemaker)
  2. Sinus node disease (except in patients with a functioning artificial pacemaker)
  3. Unstable angina
  4. Acute myocardial infarction
  5. Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)
  6. Hypersensitivity to adenosine
  7. Caffeine within 12-24 hours
  8. Theophylline and Dipyridamole products within 24 hours

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01655043

United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Astellas Pharma Global Development, Inc.
Principal Investigator: James C Carr, MD Northwestern University

Publications of Results:
Responsible Party: James Carr, director of cardiovascular imaging, Northwestern University Identifier: NCT01655043     History of Changes
Other Study ID Numbers: STU00050900
000598 ( Other Grant/Funding Number: Astellas Pharma Global Development, Inc )
First Posted: August 1, 2012    Key Record Dates
Results First Posted: March 27, 2015
Last Update Posted: April 20, 2015
Last Verified: March 2015

Keywords provided by James Carr, Northwestern University:
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Myocardial Ischemia
Coronary Artery Disease
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arterial Occlusive Diseases
Adenosine A2 Receptor Agonists
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs