Vascular DiseasesEarly Phase 1NCT00693758
Assessment of Oxygen Changes in the Heart With Cardio-vascular Magnetic Resonance Imaging
A Early Phase 1 study testing adenosine, modified end-tidal forcing system and arm cuff occlusion in people with Vascular Diseases and Myocardial Ischemia, run by University of Calgary at 1 site in Canada.
Trial summary
The ability of a new SSFP-based BOLD MRI sequence to assess myocardial oxygenation changes in response to coronary flow changes induced by adenosine and increased CO2-partial pressure will be examined in healthy volunteers and patients with suspected coronary artery disease. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vascular Diseases, Myocardial Ischemia
- What is being tested?
- adenosine, modified end-tidal forcing system and arm cuff occlusion
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2006to Sep 2011
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Informed written consent
- age > 18 years
- no known cardiovascular disease and no vasoactive medication (if recruited as healthy volunteer)
- suspected coronary artery disease or microvascular dysfunction (if recruited as patient)
- no known obstructive or restrictive lung disease
- fasting for 4 hours prior to the study
Who cannot join
- Contraindications for MRI
- Known obstructive or restrictive lung disease
- concomitant serious medical condition
Trial locations and contacts
1 site in 1 country.
Canada1 site
Stephenson CMR Centre at Foothills Medical Centre, University of Calgary
Calgary, Alberta, T2N 2T9
About this study
Official title: Magnetic Resonance Imaging for the Detection of Oxygen Changes in the Heart
The ability of a new SSFP-based BOLD MRI sequence to assess myocardial oxygenation changes in response to coronary flow changes induced by adenosine and increased CO2-partial pressure will be examined in healthy volunteers and patients with suspected coronary artery disease. Also the susceptibility of a new SSFP-based BOLD sensitive MRI sequence to changes in arterial oxygenation will be examined. This will help understand the physiologic basis of oxygen sensitive imaging of the heart.
Read the detailed description
A new SSFP based T2 and T2* sensitive sequence which provides good BOLD contrast will be used. It was developed by researchers at the Stephenson CMR Centre and Northwestern University of Chicago. Its major advantage to previous BOLD sensitive sequences is its lower susceptibility to motion artifacts.
MR imaging is performed with a commercial 1.5 T Siemens MR scanner (Siemens Avanto). In order to obtain a homogeneous magnetic field an additional surface chest coil is used in combination to the body coil. Three short axis views representing basal, mid and apical slices are set up and are used throughout the study. If the volunteer has to be moved from their position for any reason, similar short axis views will be attempted.
In order to improve and further develop the MRI sequence the technique will be used in a arm-cuff model in healthy volunteers, using reactive hyperemia, which is easier to image than the heart. The BOLD-MRI signal intensity of the forearm will be assessed during a short, 3 min. lasting upper arm-cuff occlusion and the following reactive hyperemia.
Main interest of the study is the examination of the heart of healthy volunteers as well as patients with suspected coronary heart disease with this BOLD-MRI technique. The signal intensity of the myocardium at rest and after different coronary flow stimulation will be assessed. These stimuli will be pharmacologic (adenosine) as well as changes in arterial CO2 and O2 pressure.
All subjects that will undergo changes in their breathing gases, will first be examined in the vascular research laboratory of Dr. M. Poulin. There the subjects will be familiarized with the modified end-tidal forcing system (MEFS) and their individual response to changes in breathing gases will be assessed. A complete dry-run of the breathing protocol will be performed including 2 capillary blood gas analysis. On a second day subjects will be studied in the temperature-controlled MR scanning room at Stephenson CMR Centre in a fasting state for the previous 4 hours. This includes refrain from caffeine and nicotine in these preceding 4 hours. Prior to baseline scanning, capillary blood will be sampled from the finger for blood gas, hemoglobin and hematocrit analysis. Thereafter, the volunteer will be connected to the MEFS. A baseline scan will then be performed comprising of localization, cine imaging, cross sectional flow measurement of the coronary sinus (CS) and BOLD MRI of three representative short axis slices. Then an intravenous adenosine infusion will be started. After 3 min. MR scan will be repeated. After 5 min. of rest another baseline will be recorded. Then successively the carbon dioxide pressure will be increased in two steps to 40 and 45 mmHg. After a resting period of 5 min, another baseline scan will be performed. Then oxygen partial pressure of the inspired air will be reduced in 3 steps as described in the following paragraph until an inspiratory oxygen partial pressure of 45 mmHg is achieved. This will reflect an arterial oxygen saturation of approximately 90, 85 and 80%. At each step, BOLD MRI (3 axial slices) and cross sectional flow measurements of CS will be performed. Following 5 minutes of rest another baseline scan will be performed. Throughout experimentation the subject will be connected to the METFS and we will measure ventilation, blood pressure (noninvasive), heart rate (electrocardiogram) and arterial oxygen saturation (pulse oximetry).
Image-analysis: A region of interest will be drawn around the myocardium of each short axis. The averaged signal intensity is assessed and compared to baseline after adenosine infusion and at the different levels of arterial oxygenation and carbon dioxide concentration. Additionally, differential analysis for subendocardium and subepicardium will be performed.
Coronary flow in the coronary sinus will be calculated using phase contrast MRI. This technique was first described by van Rossum, validated in phantoms and animal studies and successfully used in human patient studies. Because of the relatively small diameter of the CS, absolute flow values may not be very accurate; therefore the relative change between different levels of hypoxia will be calculated.
End-points:
BOLD SI in the myocardium defined as the averaged signal intensity of the myocardium.
Relative flow changes in CS to baseline.
- Conditions
- Vascular Diseases, Myocardial Ischemia
- Being tested
- adenosine, modified end-tidal forcing system, arm cuff occlusion, Breathing gas, Blood pressure cuff
- Keywords
- MRI, coronary reactivity, coronary physiology
- Medical subject headings
- Vascular Diseases, Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adenosineDrug
Also called Adenosine stress
intravenous infusion of adenosine (140microgr./min/kg)
modified end-tidal forcing systemOther
Also called O2 / CO2 changes in inspired air
changes in partial pressures of O2 and CO2 in inspired air
arm cuff occlusionOther
3 min. lasting upper arm cuff occlusion
Breathing gasDevice
Changes in pO2 and pCO2 in inspired air mix
Blood pressure cuffDevice
supra-systolic arm occlusion with pressure cuff
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | healthy volunteers without intervention Receives: Device: Breathing gas |
| 2 | No intervention | patients with suspected coronary artery disease without intervention |
| 3 | Experimental | Healthy volunteers during adenosine infusion Receives: Drug: adenosine; Device: Blood pressure cuff |
| 4 | Experimental | Healthy volunteers during changes of breathing gases (CO2, O2) Receives: Other: modified end-tidal forcing system |
| 5 | Experimental | patients with suspected coronary artery disease during adenosine infusion Receives: Drug: adenosine |
| 6 | Experimental | patients with suspected coronary artery disease during changes of breathing gases Receives: Other: modified end-tidal forcing system |
| 7 | Experimental | Assessment of reactive hyperemia in arms of healthy volunteers to improve sequences Receives: Other: arm cuff occlusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD-MRI signal intensity changes
Measured: 60
Secondary outcomes (1)
Flow changes
Measured: 60 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2008 (estimated)
- Study startJan 2006
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vascular DiseasesStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Oliver Strohm, University of Calgary
- Investigators
- Matthias Friedrich, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00693758
- Sponsor's protocol ID
- 18798
- Other IDs
- 18798
- Status last verified
- Oct 2011
- First submitted
- 10 Dec 2007
- Last updated
- 4 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance Imaging for the Detection of Oxygen Changes in the Heart
- ClinicalTrials.gov ID
- NCT00693758
- Acronym / sponsor ID
- 18798
- Conditions
- Vascular Diseases, Myocardial Ischemia
- Keywords
- MRI, coronary reactivity, coronary physiology
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 9 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ability of a new SSFP-based BOLD MRI sequence to assess myocardial oxygenation changes in response to coronary flow changes induced by adenosine and increased CO2-partial pressure will be examined in healthy volunteers and patients with suspected coronary artery disease. Also the susceptibility of a new SSFP-based BOLD sensitive MRI sequence to changes in arterial oxygenation will be examined. This will help understand the physiologic basis of oxygen sensitive imaging of the heart.
Detailed description
A new SSFP based T2 and T2* sensitive sequence which provides good BOLD contrast will be used. It was developed by researchers at the Stephenson CMR Centre and Northwestern University of Chicago. Its major advantage to previous BOLD sensitive sequences is its lower susceptibility to motion artifacts.
MR imaging is performed with a commercial 1.5 T Siemens MR scanner (Siemens Avanto). In order to obtain a homogeneous magnetic field an additional surface chest coil is used in combination to the body coil. Three short axis views representing basal, mid and apical slices are set up and are used throughout the study. If the volunteer has to be moved from their position for any reason, similar short axis views will be attempted.
In order to improve and further develop the MRI sequence the technique will be used in a arm-cuff model in healthy volunteers, using reactive hyperemia, which is easier to image than the heart. The BOLD-MRI signal intensity of the forearm will be assessed during a short, 3 min. lasting upper arm-cuff occlusion and the following reactive hyperemia.
Main interest of the study is the examination of the heart of healthy volunteers as well as patients with suspected coronary heart disease with this BOLD-MRI technique. The signal intensity of the myocardium at rest and after different coronary flow stimulation will be assessed. These stimuli will be pharmacologic (adenosine) as well as changes in arterial CO2 and O2 pressure.
All subjects that will undergo changes in their breathing gases, will first be examined in the vascular research laboratory of Dr. M. Poulin. There the subjects will be familiarized with the modified end-tidal forcing system (MEFS) and their individual response to changes in breathing gases will be assessed. A complete dry-run of the breathing protocol will be performed including 2 capillary blood gas analysis. On a second day subjects will be studied in the temperature-controlled MR scanning room at Stephenson CMR Centre in a fasting state for the previous 4 hours. This includes refrain from caffeine and nicotine in these preceding 4 hours. Prior to baseline scanning, capillary blood will be sampled from the finger for blood gas, hemoglobin and hematocrit analysis. Thereafter, the volunteer will be connected to the MEFS. A baseline scan will then be performed comprising of localization, cine imaging, cross sectional flow measurement of the coronary sinus (CS) and BOLD MRI of three representative short axis slices. Then an intravenous adenosine infusion will be started. After 3 min. MR scan will be repeated. After 5 min. of rest another baseline will be recorded. Then successively the carbon dioxide pressure will be increased in two steps to 40 and 45 mmHg. After a resting period of 5 min, another baseline scan will be performed. Then oxygen partial pressure of the inspired air will be reduced in 3 steps as described in the following paragraph until an inspiratory oxygen partial pressure of 45 mmHg is achieved. This will reflect an arterial oxygen saturation of approximately 90, 85 and 80%. At each step, BOLD MRI (3 axial slices) and cross sectional flow measurements of CS will be performed. Following 5 minutes of rest another baseline scan will be performed. Throughout experimentation the subject will be connected to the METFS and we will measure ventilation, blood pressure (noninvasive), heart rate (electrocardiogram) and arterial oxygen saturation (pulse oximetry).
Image-analysis: A region of interest will be drawn around the myocardium of each short axis. The averaged signal intensity is assessed and compared to baseline after adenosine infusion and at the different levels of arterial oxygenation and carbon dioxide concentration. Additionally, differential analysis for subendocardium and subepicardium will be performed.
Coronary flow in the coronary sinus will be calculated using phase contrast MRI. This technique was first described by van Rossum, validated in phantoms and animal studies and successfully used in human patient studies. Because of the relatively small diameter of the CS, absolute flow values may not be very accurate; therefore the relative change between different levels of hypoxia will be calculated.
End-points:
BOLD SI in the myocardium defined as the averaged signal intensity of the myocardium.
Relative flow changes in CS to baseline.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | Device: Breathing gashealthy volunteers without intervention |
| 2 | No intervention | –patients with suspected coronary artery disease without intervention |
| 3 | Experimental | Drug: adenosine, Device: Blood pressure cuffHealthy volunteers during adenosine infusion |
| 4 | Experimental | Other: modified end-tidal forcing systemHealthy volunteers during changes of breathing gases (CO2, O2) |
| 5 | Experimental | Drug: adenosinepatients with suspected coronary artery disease during adenosine infusion |
| 6 | Experimental | Other: modified end-tidal forcing systempatients with suspected coronary artery disease during changes of breathing gases |
| 7 | Experimental | Other: arm cuff occlusionAssessment of reactive hyperemia in arms of healthy volunteers to improve sequences |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Informed written consent
- age > 18 years
- no known cardiovascular disease and no vasoactive medication (if recruited as healthy volunteer)
- suspected coronary artery disease or microvascular dysfunction (if recruited as patient)
- no known obstructive or restrictive lung disease
Key exclusion criteria (3 listed)
- Contraindications for MRI
- Known obstructive or restrictive lung disease
- concomitant serious medical condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adenosineAlso: Adenosine stressintravenous infusion of adenosine (140microgr./min/kg) | Drug | 3, 5 |
| modified end-tidal forcing systemAlso: O2 / CO2 changes in inspired airchanges in partial pressures of O2 and CO2 in inspired air | Other | 4, 6 |
| arm cuff occlusion3 min. lasting upper arm cuff occlusion | Other | 7 |
| Breathing gasChanges in pO2 and pCO2 in inspired air mix | Device | 1 |
| Blood pressure cuffsupra-systolic arm occlusion with pressure cuff | Device | 3 |
Primary outcome
BOLD-MRI signal intensity changes
Time frame: 60
1 secondary outcome
Flow changes
Time frame: 60 min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias Friedrich, MD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing adenosine, modified end-tidal forcing system and arm cuff occlusion in people with Vascular Diseases and Myocardial Ischemia, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BOLD-MRI signal intensity changes (time frame: 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2011.