Effects of Body Mass Index on the Hyperemic Response to Regadenoson
Condition: Obesity; Endothelial Dysfunction; Decreased Vascular Flow
Study type: Interventional

Summary: 
      We will test the hypothesis that a single dose of Regadenoson will produce equivalent degrees
      of coronary hyperemia in patients of widely different body size. This will be a prospective,
      open-label, comparative trial using MRI to measure myocardial perfusion reserve (ratio of
      myocardial blood flow with vasodilator to myocardial blood flow at rest) during sequential
      administration of the coronary vasodilators adenosine and regadenoson. Non-invasive MRI
      measurements of resting myocardial blood flow, and sequential measurements of blood flow
      during adenosine infusion (weight adjusted dosing) and then blood flow during regadenoson
      infusion (single, fixed dose. Blood flow measurements will be obtained sequentially and in
      the same sequence in each subject during a two hour MRI exam. 32 subjects will be recruited
      for this study. The first 2 will be for testing of the protocol. Inclusion criteria: 2
      subjects for initial protocol evaluation, then 30 subjects with body mass index (BMI) between
      18 and 40. Exclusions are pregnancy, renal dysfunction and claustrophobia.
    

Detailed description: 
      Introduction: Regadenoson (Lexiscan) is currently recommended for use as a targeted
      vasodilator in myocardial perfusion studies and is available as a single, fixed dose for all
      patients. Here we propose to compare the hyperemic response measured with MRI in subjects
      with a wide range of BMI 18-40.

      MRI is an ideal test to compare the effects of regadenoson in patients with different body
      mass indices (BMIs). No radiation is used and multiple perfusion tests can be performed in
      close temporal sequence. Importantly, a number of researchers have shown the ability to
      obtain quantitative stress and rest myocardial blood flow values in the heart with MR
      imaging. This allows the calculation of myocardial perfusion reserve (MPR). Flow reserve
      measurements also can be done with dynamic PET, but not with SPECT. PET has the disadvantage
      of radiation exposure.

      Regadenoson may be a more desirable agent for use with MRI than is adenosine. Adenosine
      requires the use of 2 intravenous lines, and the use of either a specialized, expensive,
      MRI-compatible infusion pump to deliver the drug, or long lengths of tubing to run to a pump
      outside the scanner room. Neither solution is ideal. Regadenoson does not require any such
      pumps or the starting of a second i.v.. The work here would accomplish 2 goals: 1) to
      demonstrate the feasibility of performing quantitative MRI perfusion measurements with
      regadenoson, and 2) to test whether a single dose of regadenoson produces maximal coronary
      hyperemia across a wide range of body sizes.

      Study Design: This will be a prospective, open-label, study. The design is single group, one
      arm, 2 interventions in which we will compare MPR measured sequentially during adenosine and
      regadenoson using MRI. Non-invasive MRI measurements of resting flow, flow at adenosine
      stress, and flow at regadenoson stress will be obtained sequentially in each subject during a
      single two hour MRI exam. Each drug will be given in the same order to all subjects.

      32 subjects will be recruited for this study. The first two subjects will be imaged only with
      resting perfusion, in order to determine optimal acquisition parameters for the study, and
      will not be used in the analysis. The main outcome measure is MPR with each agent.
    

Intervention name(s): Adenosine; Regadenoson
Intervention type(s): Drug; Drug
Intervention description(s): Myocardial perfusion reserve measured with quantitative MRI during adenosine infusion (0.14 mg/kg/min x 6 minutes).; Myocardial perfusion reserve measured during regadenoson (0.4 mg/5 ml) bolus administration using quantitative perfusion MRI.
Other intervention name(s): adenoscan; Lexiscan
Intervention MeSH terms: Adenosine; Regadenoson
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic
Keywords: adenosine; regadenoson; adenosine receptor subtypes