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Effects of Body Mass Index on the Hyperemic Response to Regadenoson

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ClinicalTrials.gov Identifier: NCT00859833
Recruitment Status : Completed
First Posted : March 11, 2009
Results First Posted : May 24, 2011
Last Update Posted : May 24, 2011
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by:
University of Utah

Tracking Information
First Submitted Date  ICMJE March 10, 2009
First Posted Date  ICMJE March 11, 2009
Results First Submitted Date  ICMJE November 1, 2010
Results First Posted Date  ICMJE May 24, 2011
Last Update Posted Date May 24, 2011
Study Start Date  ICMJE February 2009
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2011)
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 ]
The ratio of myocardial blood flow during stress (with each vasodilator) divided by the myocardial flood flow at rest = myocardial perfusion reserve (MPR)
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2009)
Coronary flow reserve measured by quantitative perfusion MRI. [ Time Frame: 12 months ]
Change History Complete list of historical versions of study NCT00859833 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Body Mass Index on the Hyperemic Response to Regadenoson
Official Title  ICMJE Effects of Body Mass Index on the Hyperemic Response to Regadenoson
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Obesity
  • Endothelial Dysfunction
  • Decreased Vascular Flow
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Adenosine
  • Drug: Regadenoson
Publications * DiBella EV, Fluckiger JU, Chen L, Kim TH, Pack NA, Matthews B, Adluru G, Priester T, Kuppahally S, Jiji R, McGann C, Litwin SE. The effect of obesity on regadenoson-induced myocardial hyperemia: a quantitative magnetic resonance imaging study. Int J Cardiovasc Imaging. 2012 Aug;28(6):1435-44. doi: 10.1007/s10554-011-9949-4. Epub 2011 Oct 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 20, 2011)
30
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2009)
32
Actual Study Completion Date  ICMJE July 2010
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 88 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00859833
Other Study ID Numbers  ICMJE 31431
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sheldon Litwin, M.D., Professor of Medicine, University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE Astellas Pharma Inc
Investigators  ICMJE
Principal Investigator: Sheldon E Litwin, MD University of Utah
PRS Account University of Utah
Verification Date May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP