Heart FailurePhase 3NCT02043522
123I-mIBG SPECT Imaging
A Phase 3 study testing Radioisotope in people with Heart Failure and Coronary Artery Disease, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
Trial summary
This study is being done with a radioisotope, 123I-mIBG (Adreview), to develop a nuclear diagnostic imaging test for patients with decreased heart function which can be used to predict the progression of the heart disease and provide the appropriate clinical treatment. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Heart Failure, Coronary Artery Disease
- What is being tested?
- Radioisotope
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2013to Nov 2015
- Phase
- Phase 3
- 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
- For all participants:
- Male or female ≥ 18 years at study entry.
- Able and willing to comply with the study procedures.
- Written informed consent.
- Female subjects must be post-menopausal, surgically sterilized or have negative serum beta human chorionic gonadotropin pregnancy test at initial screening and maintain effective contraceptive methods throughout the trial and for 30 days following the end of dosing.
- For participants with coronary artery disease and documented myocardial infarction:
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- Diagnosis of coronary artery disease (CAD) based on one or more of the following: documented myocardial infarction, significant obstructive CAD on invasive or computed tomography (CT) coronary angiography or abnormal stress perfusion study consistent with ischemia or scar
- LV ejection fraction >40% on non-invasive imaging or invasive LV angiography.
- NYHA Class 0, I or II heart failure symptoms.
- For participants with nonischemic cardiomyopathy and LV ejection fraction between 30 and 40%:
- 5. Diagnosis of NYHA Class II - III heart failure. 6. No evidence of significant obstructive CAD on invasive coronary angiography or noninvasive stress imaging 7. Resting LV ejection fraction <40% on noninvasive imaging within 30 days of research cardiac MIBG imaging 8. Current stable treatment regimen of medications including a betablocker and either an ACE inhibitor or ARB unless documented to be intolerant to these classes of drugs.
- 9. Clinically stable from at least 7 days prior to enrollment to the study to the time of the cardiac MIBG imaging.
- For control participants:
- 5. Low likelihood of CAD and a normal stress myocardial perfusion study or stress echocardiogram within 6 months of study entry.
- 6. No significant CAD: defined as stenosis >30% narrowing on invasive or CT coronary angiography within 6 months of study entry.
Who cannot join
- Previously received 123I-mIBG or 131I-mIBG.
- Participation in any other investigational product or medical device study within 30 days of enrollment.
- History or suspicion of significant allergic reaction or anaphylaxis to iodine or iodinated imaging agents.
- Poorly controlled hypertension (>180 mmHg systolic or >110 mmHg diastolic) based on measurements made during the preceding 6 months.
- Use of medications for non-cardiac medical conditions that are known to interfere with 123I-mIBG uptake and these medications cannot be safely withheld for at least 24 hours before study procedures.
- Cardiac revascularization, insertion of an ICD or an acute myocardial infarction within the past 30 days.
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- Serious non-cardiac medical condition associated with significant elevation of plasma catecholamines including pheochromocytoma.
- Claustrophobia or movement disorders that prevent the participant from lying still in a supine position for up to an hour at a time.
- Renal insufficiency (serum creatinine >3.0 mg/dL or >265 mmol/L).
- Diagnosis of or signs or symptoms of a neurologic disease such as Parkinson's disease, multiple systems atrophy or Parkinsonian syndromes, or other diseases known to affect the sympathetic nervous system.
- Breastfeeding or pregnancy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Optimization of Cardiac Iodine-123 Meta-iodobenzylguanidine (123I-mIBG) SPECT Imaging
This study is being done with a radioisotope, 123I-mIBG (Adreview), to develop a nuclear diagnostic imaging test for patients with decreased heart function which can be used to predict the progression of the heart disease and provide the appropriate clinical treatment. The types of patients to be studied include patients who have had a heart attack where heart muscle may be damaged and patients diagnosed with heart failure who have enlarged hearts. Both conditions may cause poor muscle contraction and disturbances in electrical signal conduction. There will also be a control group of participants with no evidence of heart disease.
123I-mIBG has been shown to be effective in assessing the areas of the heart being activated involuntarily by the sympathetic nervous system (SNS). 123I-mIBG is an iodine based radioisotope that is chemically similar to norepinephrine (NE) in the heart. NE is responsible for the way the SNS regulates heart functions such as heart rate and the force of heart contractions. NE acts automatically to maintain a homeostasis or balance within the SNS. The amount of 123I-mIBG, mimicking NE, that appears on the nuclear image using the heart-to-mediastinum ratio (H/M ratio), was predictive of the progression of heart failure, arrhythmias (irregular heartbeats) and cardiac death.
Two different types of single photon emission computed tomography (SPECT) imaging will be used: standard SPECT and cadmium-zinc-telluride (CZT) SPECT. The investigators hypothesize that CZT SPECT will have greater H/M ratios than standard SPECT imaging.
Read the detailed description
123I-mIBG (MIBG) cardiac scintigraphy can be used to assess cardiac sympathetic activity and predicts prognosis in patients with heart failure. The results of prognostic studies were validated in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) trial, which was a large multi-centre prospective international study of 961 patients with NYHA Class II - III Heart Failure and LV ejection fraction > 35%2. This landmark study used planar imaging for calculation of the heart-to-mediastinal ratio (H/M) as a quantitative analysis of global uptake. The H/M on 4 hour delayed planar imaging was predictive of heart failure progression, arrhythmic events and cardiac death and provided incremental value to B-type natriuretic peptide and left ventricular (LV) ejection fraction.
In a study using quantitative MIBG SPECT, a new method for the calculation of the H/M ratio was developed, compared several reconstruction methods and demonstrated that the H/M ratio from SPECT was equivalent to the planar H/M ratio for differentiating normal participants from heart failure patients.
The ability of SPECT imaging to provide more accurate quantitative measurement of myocardial activity may also provide more accurate measurements of MIBG washout, which has been shown to be predictive of sudden cardiac death using planar imaging. SPECT imaging also can provide information about the regional distribution of MIBG, which has been demonstrated to be predictive of sudden cardiac death. Similarly, mismatch of regional MIBG uptake and perfusion reflecting deinnervation of viable tissue may identify myocardium with potential for development of ventricular arrhythmias. Thus, SPECT MIBG imaging may provide much useful prognostic information in addition to the H/M ratio.
Participants will have a single dose of the isotope and the H/M ratio will be measured using 3 types of imaging techniques with cameras and software currently used at the University of Ottawa Heart Institute:
- Planar (2D) imaging, as used in the ADMIRE-HF trial
- Hawkeye Infinia 3D SPECT imaging, which is conventional SPECT
- Discovery NM-530 CZT 3D SPECT imaging, a newer SPECT technology
Images will be taken at predetermined time points over a 5 hour period on the study /injection day. Participants will be monitored for any clinical changes with routine lab work and physical observations during the study.
- Conditions
- Heart Failure, Coronary Artery Disease
- Being tested
- Radioisotope
- Keywords
- 123I-mIBG, SPECT Imaging, Phantom imaging, Heart failure, Coronary artery disease, Heart to mediastinum ratios, heart to calibration ratios, Myocardial blood flow, Myocardial blood flow researve
- Medical subject headings
- Heart Failure, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadioisotopeDrug
Also called Adreview
One dose of 10 mCi (370 mBq:± 10%, calibrated to time of injection) of 123I-mIBG (AdreView) administered as a single intravenous bolus over 1 or 2 minutes, followed by a saline flush.
| Study group | Role | What they receive |
|---|---|---|
| Nuclear Imaging | Experimental | Planar, conventional SPECT imaging and CZT SPECT imaging will be done. Imaging will begin immediately following radioisotope injection with CZT SPECT imaging for 15 minutes, followed by 1) planar anterior view imaging for 10 minutes, 2) conventional SPECT imaging for 12.5 minutes and 3) CZT SPECT imaging for 12 minutes. A low dose CT transmission scan will be acquired for attenuation correction (GE Infinia Hawkeye) with the initial conventional SPECT imaging and not repeated with subsequent imaging. Participants will undergo repeat imaging at 1, 2, 3 and 4 hours after radiotracer injection with each imaging session to include 1) planar anterior, 2) conventional SPECT and 3) CZT SPECT imaging. Receives: Drug: Radioisotope |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of heart to calibration ratios (HCR) in planar, conventional SPECT and CZT SPECT imaging
Measurements of heart to calibration ratios (HCR) in a phantom model with planar, conventional SPECT and CZT SPECT imaging will be compared between the modalities and used to set up the imaging process; Measurements of heart to mediastinum (H/M) ratios with planar, conventional SPECT and CZT SPECT imaging in participants from three specific populations on all sets of images will be compared.
Measured: Phantom image modalities will be assessed prior to human studies. Imaging studies will be done starting post injection and at hourly intervals x 4. Imaging and analysis will be complete in 5 years.
Secondary outcomes (1)
123I-mIBG clearance rates
Measurement of 123I-mIBG clearance rates in a phantom model with planar, conventional SPECT and CZT SPECT imaging will be done prior to human studies to set up the imaging settings and process.
Measurement of clearance rates 123I-mIBG of with planar, conventional SPECT and CZT SPECT in participants from three specific populations on all sets of images will be done and compared.
Measurements of segmental H/M and clearance rates in a phantom model and in participants including the 3 specific populations with acquisitions using planar, conventional SPECT and CZT SPECT imaging will be done at the same time as the other image analysis data sets.
Measured: Phantom image modalities will be assessed prior to human studies. Imaging studies will be done starting post injection and at hourly intervals x 4. Imaging and analysis will be complete in 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2014 (estimated)
- Study startDec 2013
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- 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
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- GE Healthcare
- Responsible party
- Principal investigator, Terrence Ruddy, Ottawa Heart Institute Research Corporation
- Investigators
- Terrence D Ruddy, MD, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02043522
- Sponsor's protocol ID
- 20130692
- Status last verified
- Apr 2017
- First submitted
- 6 Jan 2014
- Last updated
- 24 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, Agostini D, Weiland F, Chandna H, Narula J; ADMIRE-HF Investigators. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010 May 18;55(20):2212-21. doi: 10.1016/j.jacc.2010.01.014. Epub 2010 Feb 25.
PubMed 20188504
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Cardiac Iodine-123 Meta-iodobenzylguanidine (123I-mIBG) SPECT Imaging
- ClinicalTrials.gov ID
- NCT02043522
- Acronym / sponsor ID
- 20130692
- Conditions
- Heart Failure, Coronary Artery Disease
- Keywords
- 123I-mIBG, SPECT Imaging, Phantom imaging, Heart failure, Coronary artery disease, Heart to mediastinum ratios, heart to calibration ratios, Myocardial blood flow
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Collaborators
- GE Healthcare
- Study start
- Dec 2013
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 23 Jan 2014 (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.
This study is being done with a radioisotope, 123I-mIBG (Adreview), to develop a nuclear diagnostic imaging test for patients with decreased heart function which can be used to predict the progression of the heart disease and provide the appropriate clinical treatment. The types of patients to be studied include patients who have had a heart attack where heart muscle may be damaged and patients diagnosed with heart failure who have enlarged hearts. Both conditions may cause poor muscle contraction and disturbances in electrical signal conduction. There will also be a control group of participants with no evidence of heart disease.
123I-mIBG has been shown to be effective in assessing the areas of the heart being activated involuntarily by the sympathetic nervous system (SNS). 123I-mIBG is an iodine based radioisotope that is chemically similar to norepinephrine (NE) in the heart. NE is responsible for the way the SNS regulates heart functions such as heart rate and the force of heart contractions. NE acts automatically to maintain a homeostasis or balance within the SNS. The amount of 123I-mIBG, mimicking NE, that appears on the nuclear image using the heart-to-mediastinum ratio (H/M ratio), was predictive of the progression of heart failure, arrhythmias (irregular heartbeats) and cardiac death.
Two different types of single photon emission computed tomography (SPECT) imaging will be used: standard SPECT and cadmium-zinc-telluride (CZT) SPECT. The investigators hypothesize that CZT SPECT will have greater H/M ratios than standard SPECT imaging.
Detailed description
123I-mIBG (MIBG) cardiac scintigraphy can be used to assess cardiac sympathetic activity and predicts prognosis in patients with heart failure. The results of prognostic studies were validated in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) trial, which was a large multi-centre prospective international study of 961 patients with NYHA Class II - III Heart Failure and LV ejection fraction > 35%2. This landmark study used planar imaging for calculation of the heart-to-mediastinal ratio (H/M) as a quantitative analysis of global uptake. The H/M on 4 hour delayed planar imaging was predictive of heart failure progression, arrhythmic events and cardiac death and provided incremental value to B-type natriuretic peptide and left ventricular (LV) ejection fraction.
In a study using quantitative MIBG SPECT, a new method for the calculation of the H/M ratio was developed, compared several reconstruction methods and demonstrated that the H/M ratio from SPECT was equivalent to the planar H/M ratio for differentiating normal participants from heart failure patients.
The ability of SPECT imaging to provide more accurate quantitative measurement of myocardial activity may also provide more accurate measurements of MIBG washout, which has been shown to be predictive of sudden cardiac death using planar imaging. SPECT imaging also can provide information about the regional distribution of MIBG, which has been demonstrated to be predictive of sudden cardiac death. Similarly, mismatch of regional MIBG uptake and perfusion reflecting deinnervation of viable tissue may identify myocardium with potential for development of ventricular arrhythmias. Thus, SPECT MIBG imaging may provide much useful prognostic information in addition to the H/M ratio.
Participants will have a single dose of the isotope and the H/M ratio will be measured using 3 types of imaging techniques with cameras and software currently used at the University of Ottawa Heart Institute:
- Planar (2D) imaging, as used in the ADMIRE-HF trial
- Hawkeye Infinia 3D SPECT imaging, which is conventional SPECT
- Discovery NM-530 CZT 3D SPECT imaging, a newer SPECT technology
Images will be taken at predetermined time points over a 5 hour period on the study /injection day. Participants will be monitored for any clinical changes with routine lab work and physical observations during the study.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nuclear Imaging | Experimental | Drug: RadioisotopePlanar, conventional SPECT imaging and CZT SPECT imaging will be done. Imaging will begin immediately following radioisotope injection with CZT SPECT imaging for 15 minutes, followed by 1) planar anterior view imaging for 10 minutes, 2) conventional SPECT imaging for 12.5 minutes and 3) CZT SPECT imaging for 12 minutes. A low dose CT transmission scan will be acquired for attenuation correction (GE Infinia Hawkeye) with the initial conventional SPECT imaging and not repeated with subsequent imaging. Participants will undergo repeat imaging at 1, 2, 3 and 4 hours after radiotracer injection with each imaging session to include 1) planar anterior, 2) conventional SPECT and 3) CZT SPECT imaging. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Male or female ≥ 18 years at study entry.
- Able and willing to comply with the study procedures.
- Written informed consent.
- Female subjects must be post-menopausal, surgically sterilized or have negative serum beta human chorionic gonadotropin pregnancy test at initial screening and maintain effective contraceptive methods throughout the trial and for 30 days following the end of dosing.
- Diagnosis of coronary artery disease (CAD) based on one or more of the following: documented myocardial infarction, significant obstructive CAD on invasive or computed tomography (CT) coronary angiography or abnormal stress perfusion study consistent with ischemia or scar
Key exclusion criteria (11 listed)
- Previously received 123I-mIBG or 131I-mIBG.
- Participation in any other investigational product or medical device study within 30 days of enrollment.
- History or suspicion of significant allergic reaction or anaphylaxis to iodine or iodinated imaging agents.
- Poorly controlled hypertension (>180 mmHg systolic or >110 mmHg diastolic) based on measurements made during the preceding 6 months.
- Use of medications for non-cardiac medical conditions that are known to interfere with 123I-mIBG uptake and these medications cannot be safely withheld for at least 24 hours before study procedures.
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 |
|---|---|---|
| RadioisotopeAlso: AdreviewOne dose of 10 mCi (370 mBq:± 10%, calibrated to time of injection) of 123I-mIBG (AdreView) administered as a single intravenous bolus over 1 or 2 minutes, followed by a saline flush. | Drug | Nuclear Imaging |
Primary outcome
Comparison of heart to calibration ratios (HCR) in planar, conventional SPECT and CZT SPECT imaging
Time frame: Phantom image modalities will be assessed prior to human studies. Imaging studies will be done starting post injection and at hourly intervals x 4. Imaging and analysis will be complete in 5 years.
Measurements of heart to calibration ratios (HCR) in a phantom model with planar, conventional SPECT and CZT SPECT imaging will be compared between the modalities and used to set up the imaging process; Measurements of heart to mediastinum (H/M) ratios with planar, conventional SPECT and CZT SPECT imaging in participants from three specific populations on all sets of images will be compared.
1 secondary outcome
123I-mIBG clearance rates
Time frame: Phantom image modalities will be assessed prior to human studies. Imaging studies will be done starting post injection and at hourly intervals x 4. Imaging and analysis will be complete in 5 years.
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 24 Apr 2017.
- Background: PubMed 20188504Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, Agostini D, Weiland F, Chandna H, Narula J; ADMIRE-HF Investigators. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010 May 18;55(20):2212-21. doi: 10.1016/j.jacc.2010.01.014. Epub 2010 Feb 25.
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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.
Terrence D Ruddy, MD principal investigator
Ottawa Heart Institute Research Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Radioisotope in people with Heart Failure and Coronary Artery Disease, run by Ottawa Heart Institute Research Corporation 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 15 inclusion and 11 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 24 Apr 2017. 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Comparison of heart to calibration ratios (HCR) in planar, conventional SPECT and CZT SPECT imaging (time frame: Phantom image modalities will be assessed prior to human studies. Imaging studies will be done starting post injection and at hourly intervals x 4. Imaging and analysis will be complete in 5 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02043522, which also lists 1 linked publication.
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 24 Apr 2017; AzTrials last refreshed its copy on 29 Oct 2026.