Effects of Body Mass Index on the Hyperemic Response to Regadenoson

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by:
University of Utah
ClinicalTrials.gov Identifier:
NCT00859833
First received: March 10, 2009
Last updated: May 20, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention
Obesity
Endothelial Dysfunction
Decreased Vascular Flow
Drug: Adenosine
Drug: Regadenoson

Study Type: Interventional
Study Design: Endpoint Classification: Bio-equivalence Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Diagnostic
Official Title: Effects of Body Mass Index on the Hyperemic Response to Regadenoson

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Myocardial Perfusion Reserve Measured by Quantitative Perfusion MRI (Ratio of Myocardial Blood Flow During Stress Over Myocardial Blood Flow at Rest) [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    The ratio of myocardial blood flow during stress (with each vasodilator) divided by the myocardial flood flow at rest = myocardial perfusion reserve (MPR)


Enrollment: 30
Study Start Date: February 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: myocardial perfusion reserve
Myocardial perfusion reserve will be measured by quantifying myocardial blood flow using MRI at rest and then with each of 2 coronary vasodilators. Measurements are performed with first pass gadolinium perfusion (i.v. bolus injection of 0.02 or 0.03 mmol/kg of gadolinium). Each of the 2 drugs is given sequentially (30 minutes apart) in the same sequence in every patient. The shorter acting drug (adenosine) is given first so it has time to wear off before giving the second drug. It is ideal to measure MPR with each drug during the same imaging session so that there are no other clinical variables that change between the administration of the 2 agents. See below.
Drug: Adenosine
Myocardial perfusion reserve measured with quantitative MRI during adenosine infusion (0.14 mg/kg/min x 6 minutes).
Other Name: adenoscan
Drug: Regadenoson
Myocardial perfusion reserve measured during regadenoson (0.4 mg/5 ml) bolus administration using quantitative perfusion MRI.
Other Name: Lexiscan

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.

  Eligibility

Ages Eligible for Study:   18 Years to 88 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • BMI 20-40 kg/m^2
  • age 18-88

Exclusion Criteria:

  • critically ill patients, patients on ventilators, patients with hypotension, asthmatics, and other patients whose medical care or safety may be compromised from undergoing an MRI examination will be excluded.
  • Patients with claustrophobia will also be excluded.
  • Also, anyone with contraindications to MRI (pacemaker, ICD, metal implants), pregnant subjects, minors, and prisoners will be excluded from this study.
  • If subjects are over 60 or have any suspicion of abnormal kidney function, a blood test to determine GFR will be performed prior to imaging.
  • Subjects with GFR < 30 will be excluded from the study.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00859833

Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
Astellas Pharma Inc
Investigators
Principal Investigator: Sheldon E Litwin, MD University of Utah
  More Information

No publications provided by University of Utah

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sheldon Litwin, M.D., Professor of Medicine, University of Utah
ClinicalTrials.gov Identifier: NCT00859833     History of Changes
Other Study ID Numbers: 31431
Study First Received: March 10, 2009
Results First Received: November 1, 2010
Last Updated: May 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
adenosine
regadenoson
adenosine receptor subtypes

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Adenosine
Regadenoson
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Vasodilator Agents
Adenosine A2 Receptor Antagonists
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014