Absolute Quantification of Coronary Flow Reserve by Stress Perfusion MRI

August 16, 2019 updated by: James Carr, Northwestern University

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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 Names:
  • Lexiscan
Drug: gadofoveset trisodium
All subjects to receive 5 ml IV gadofoveset trisodium contrast (Ablavar) at both stress and rest.
Other Names:
  • Ablavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
outcome measured following single MRI scan

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

Astellas Pharma Global Development, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

July 30, 2012

First Submitted That Met QC Criteria

July 31, 2012

First Posted (Estimate)

August 1, 2012

Study Record Updates

Last Update Posted (Actual)

August 28, 2019

Last Update Submitted That Met QC Criteria

August 16, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00050900
  • 000598 (Other Grant/Funding Number: Astellas Pharma Global Development, Inc)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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