CO2 as a Stress Agent for Perfusion Imaging (CO2 STRESS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Ottawa Heart Institute
Sponsor:
Information provided by (Responsible Party):
Terrence Ruddy, University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:
NCT02043535
First received: January 3, 2014
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

Myocardial perfusion imaging (MPI) is a nuclear scan using a radioisotope to see blood flow to the muscles of the heart when the heart is at rest and when it is under stress. The stress test in MPI can be done using medications, such as adenosine, that dilate coronary arteries and increase blood flow. Similarly, elevated carbon dioxide (CO2) levels in the blood, or hypercapnia, also dilates arteries and increases blood flow. Thornhill Research Inc. has developed the RespirAct ™ Gen4 sequential gas delivery system used to control CO2 levels in the blood. The RespirAct ™ Gen4 can deliver precise amounts of CO2 through a mouthpiece for inhalation to increase CO2 levels in the blood and thereby increasing blood flow like during stress.

The objective of this study is to compare the differences in blood flow through the arteries of the heart during stress with hypercapnia and adenosine MPI. The imaging will be done using positron emission tomography (PET) with the radioisotope, or tracer, called Rubidium (Rb-82). The Rb-82 is given through a pump, or elution system.

The investigators hypothesize that hypercapnia will induce a stress-to-rest increase in myocardial blood flow by a factor of 2 or more in myocardial regions supplied by non-stenotic arteries in normal volunteers and participants with coronary artery disease.


Condition Intervention
Coronary Artery Disease
Device: Delivery of precise levels of carbon dioxide with the RespirAct™ Gen4 sequential gas delivery system
Device: Delivery of rubidium radioisotope (Rb-82) using the automated pump/elution system

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effects of Controlled Hypercapnic Stimulation on Myocardial Blood Flow Measured With Positron Emission Tomography

Resource links provided by NLM:


Further study details as provided by University of Ottawa Heart Institute:

Primary Outcome Measures:
  • Myocardial blood flow differences [ Time Frame: Difference between baseline rest scan blood flow and hypercapnia stress scan myocardial blood flow at 50 mmHg, 55 mmHg, 60 mmHg levels from baseline. Imaging and intervention analysis will be complete in 4 years. ] [ Designated as safety issue: No ]
    The myocardial blood flow (MBF) will be quantified with each Rb-82 PET scan done. Polar-maps representing MBF are generated for each rest and stress state using in-house FlowQuant©software. The rest scan will be the baseline. The myocardial blood flow in the four stress scans using hypercapnia as a stress agent will be compared to the rest baseline myocardial blood flow and the adenosine stress scan myocardial blood flow.


Secondary Outcome Measures:
  • Absolute myocardial blood flow differences between end-tidal CO2 scans [ Time Frame: Difference between baseline and 60 mmHg PetCO2. Imaging and intervention analysis will be complete in 4 years. ] [ Designated as safety issue: No ]
    The effect of increasing doses of pulmonary end-tidal carbon dioxide tension (PetCO2) will be measured and quantification of absolute myocardial blood flow using Rb-82 PET will be calculated. Polar-maps representing MBF are generated for each stress state using in-house FlowQuant©software. Five levels will be measured.

  • Difference bewteen absolute myocardial blood flow with hypercapnia and with adenosine stress. [ Time Frame: Quantification and comparison of the differences in myocardial blood flow with adenosine stress and increasing levels of CO2 as a stress agent. Imaging and intervention analysis will be complete in 4 years. ] [ Designated as safety issue: No ]
    The effects of hypercapnia and adenosine on absolute myocardial blood flow using Rb-82 PET will be compared. Polar-maps representing MBF are generated for each stress state using in-house FlowQuant©software.


Estimated Enrollment: 60
Study Start Date: March 2014
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Myocardial blood flow quantification

RespirAct ™ Gen4 Sequential gas delivery breathing circuit: delivery of CO2 in increasing levels.

Rubidium Elution System: delivery of Rb-82 through an automated pump system for myocardial PET perfusion imaging.

Adenosine stress myocardial PET perfusion imaging: as a standard for comparison.

Device: Delivery of precise levels of carbon dioxide with the RespirAct™ Gen4 sequential gas delivery system

All participants will undergo a baseline rest Rb-82 positron emission tomography (PET) myocardial perfusion imaging scan (MPI) with low-dose computed tomography. Following this baseline study, serial Rb-82 PET MPI using three target levels of carbon dioxide (CO2) (50 mmHg, 55 mmHg, and 60 mmHg (± 3 mmHg)) as a stress agent will be performed. The 60 mmHg level will be repeated following a minimum 10 minute rest. A rest/stress Rb-82 PET MPI will be performed after return to normal CO2 levels (normocapnea) using adenosine as the stress agent.

Myocardial perfusion stress testing

Other Name: RespirAct™ Gen4
Device: Delivery of rubidium radioisotope (Rb-82) using the automated pump/elution system
All participants will undergo a baseline rest Rb-82 positron emission tomography myocardial perfusion imaging scan (PET MPI) with low-dose CT. Following this baseline study, serial Rb-82 PET MPI using three target levels of pulmonary end-tidal carbon dioxide tension (PetCO2) (50 mmHg, 55 mmHg, and 60 mmHg (± 3 mmHg)) as a stress agent will be performed. The 60 mmHg level will be repeated following a minimum 10 minute rest. A second rest Rb-82 PET MPI will be performed after return to normocapnea, followed by a pharmacologic adenosine stress Rb-82 PET MPI.
Other Name: Ruby-Fill™

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For all participants

  • Age ≥ 18 years old
  • BMI ≤ 40 kg/m2
  • Able and willing to comply with the study procedures
  • Written informed consent
  • Participants with documented coronary artery disease
  • Stable coronary artery disease on a stable medication regime.
  • Healthy volunteers without known heart disease
  • Low risk of coronary artery disease (CAD)

Exclusion Criteria:

  • History or risk of severe bradycardia (heart rate < 50 beats per minute) not related to chronotropic drugs
  • Known second- or third-degree Atrio-ventricular block without pacemaker
  • Atrial flutter or atrial fibrillation
  • Dyspnea (NYHA III/IV), wheezing asthma or Chronic Obstructive Pulmonary Disease (COPD)
  • Coronary artery bypass graft (CABG) surgery within 60 days prior to screening or at any time after consent
  • Percutaneous coronary intervention (PCI) within 30 days prior to screening or at any time following consent
  • Acute myocardial infarction or acute coronary syndrome within 60 days prior to screening or at any time following consent
  • Recent use of dipyridamole, dipyridamole-containing medications (e.g. Aggrenox)
  • Known hypersensitivity to adenosine
  • Breastfeeding or pregnancy
  • Claustrophobia or inability to lie still in a supine position
  • Unwillingness or inability to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02043535

Contacts
Contact: Marlie Poirier, BScN, CCRP 613-761-5103 mpoirier@ottawaheart.ca
Contact: Farrah Ahmed 613-798-5555 ext 12697 fahmed@ottawaheart.ca

Locations
Canada, Ontario
University Of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Principal Investigator: Terrence D Ruddy, MD         
Sponsors and Collaborators
University of Ottawa Heart Institute
Investigators
Principal Investigator: Terrence D Ruddy, MD University of Ottawa Heart Institute
  More Information

No publications provided

Responsible Party: Terrence Ruddy, MD, University of Ottawa Heart Institute
ClinicalTrials.gov Identifier: NCT02043535     History of Changes
Other Study ID Numbers: 20140012
Study First Received: January 3, 2014
Last Updated: August 13, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of Ottawa Heart Institute:
myocardial perfusion imaging
myocardial blood flow
pharmacologic stress agents
carbon dioxide
rubidium 82 radioisotope
positron emission tomography

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 18, 2014