Overview

This trial is active, not recruiting.

Condition coronary artery disease
Treatments delivery of precise levels of carbon dioxide with the respiract™ gen4 sequential gas delivery system, delivery of rubidium radioisotope (rb-82) using the automated pump/elution system
Sponsor Ottawa Heart Institute Research Corporation
Start date March 2014
End date February 2017
Trial size 60 participants
Trial identifier NCT02043535, 20140012

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose diagnostic
Arm
(Other)
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.
delivery of precise levels of carbon dioxide with the respiract™ gen4 sequential gas delivery system RespirAct™ Gen4
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
delivery of rubidium radioisotope (rb-82) using the automated pump/elution system Ruby-Fill™
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.

Primary Outcomes

Measure
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.

Secondary Outcomes

Measure
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.
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.

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Effects of Controlled Hypercapnic Stimulation on Myocardial Blood Flow Measured With Positron Emission Tomography
Principal investigator Terrence D Ruddy, MD
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Ottawa Heart Institute Research Corporation.