Ischemic CardiomyopathyNCT01919983
Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death
An observational study of Ischemic Cardiomyopathy and Dilated Cardiomyopathy, run by Johns Hopkins University at 1 site in United States.
Trial summary
Despite pharmacologic advances for the treatment of congestive heart failure (HF), sudden cardiac death (SCD) and pump failure remain the leading causes of mortality in patients with HF. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Cardiomyopathy, Dilated Cardiomyopathy, Inflammation
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Sep 2014
- Phase
- Observational
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a cardiomyopathy with an LVEF ≤35% who have undergone placement of an implantable cardioverter-defibrillator for primary prevention of sudden cardiac death
Patient Population - This proposal will enroll patients from the PROSE-ICD cohort who have undergone ICD implantation for primary prevention of SCD. PROSE-ICD is a multicenter prospective observational cohort study designed to identify risk factors for SCD in high-risk patients.
Inclusion Criteria The entire PROSE-ICD population with ischemic and non-ischemic cardiomyopathy will be divided into quartiles based on previously measured hsCRP levels in the PROSE-ICD database. The study sample for this study will include 50 randomly selected PROSE-ICD participants from the lowest hsCRP quartile and another 50 randomly selected participants from the highest quartile. PROSE-ICD includes patients greater than 18 years old who have a history of acute MI at least 4 weeks old (confirmed by persistent pathologic Q waves on ECG, CPK-MB > three times the upper limit of normal, or a fixed perfusion defect on nuclear imaging) or non-ischemic LV dysfunction for at least 9 months who have an EF ≤ 35% and who have undergone implantation of an FDA-approved ICD for primary prevention of SCD within 2 weeks of enrollment.
Exclusion Criteria Exclusion criteria for PROSE-ICD include an indication for ICD implantation for secondary prevention; inability or unwillingness to provide informed consent; women <50 years old with anatomic child-bearing potential who are unwilling to use contraceptives; NYHA class IV HF; patients with permanent pacemakers; and unsuccessful ICD implantation
Additional exclusion criteria for PROSE-ICD patients enrolled in MIBG imaging will include:
- Positive pregnancy test in women with child bearing potential
- Use of a medication for non-cardiac conditions that may interfere with MIBG that cannot be safely withheld for five half-lives before study procedures.
- Renal insufficiency (GFR <30 ml/dl or creatinine >3.0 mg/dl) or dialysis.
- Hypersensitivity to iodine.
Trial locations and contacts
1 site in 1 country.
About this study
Despite pharmacologic advances for the treatment of congestive heart failure (HF), sudden cardiac death (SCD) and pump failure remain the leading causes of mortality in patients with HF. Although, SCD is poorly understood, implantable cardiac defibrillators (ICD) have been shown to be an effective, but costly therapy in preventing SCD. At present, left ventricular systolic dysfunction is our best independent predictor of SCD, but only moderately predicts those patients who will eventually benefit from the placement of an ICD and, in most cases, left ventricular (LV) systolic dysfunction is a non-modifiable risk factor once acquired. As a result, there exists an intensive search for biomarkers that could improve the prediction of SCD and have the potential for risk factor modification.
Experimental and clinical evidence has established that inflammation plays a critical role in stable coronary disease, plaque rupture, acute myocardial infarction, heart failure, and SCD. Studies at our institution have demonstrated that elevated levels of hsCRP and Interleukin-6 are predictive of arrhythmic SCD; however, the mechanism of causing this increased risk is unclear.
Read more
Another well-known risk factor for SCD is abnormal sympathetic innervation. The most robust clinical test of sympathetic innervation to date is Iodine-123 Metaiodobenzylguanidine (MIBG) imaging with gamma scintigraphy. MIBG imaging has emerged as one of our strongest predictors of SCD by detecting sympathetic nervous system abnormalities in patients with HF. Preclinical and clinical evidence suggests that myocardial inflammation adversely affects myocardial innervation.
Based on these findings, the investigators hypothesize that elevated levels of inflammatory biomarkers are associated with abnormal sympathetic innervation as measured by MIBG imaging. The investigators aim to establish the strength of this association. This proposal will leverage unique access to the largest, most extensively phenotyped cohort of patients who have undergone ICD implantation for primary prevention of SCD, the PRospective Observational Study of the ICD in SCD, (PROSE-ICD).
Read the detailed description
The primary aim is as follows:
Primary Aim 1: Determine if inflammation is associated with abnormal cardiac sympathetic innervation in patients enrolled in the PROSE-ICD study.
Rationale/Hypothesis: The investigators hypothesize that patients with increased biomarkers of systemic inflammation have abnormal cardiac sympathetic innervation as measured by MIBG imaging.
Specifically the investigators will: Image 100 patients from the PROSE-ICD cohort, 50 each from the highest and lowest quartiles of hsCRP levels and determine whether patients with biomarker evidence of increased inflammation also have abnormal sympathetic innervation.
In addition, the investigators will pursue the following secondary aims:
- Determine if inflammation, measured by IL-6, is associated with abnormal cardiac sympathetic innervation, measured by MIBG imaging, in patients enrolled in the PROSE-ICD study.
- Examine the association of CRP and MIBG with ICD therapies in PROSE-ICD.
- Compare several MIBG imaging metrics of sympathetic innervation, in addition to the late H/M ratio, including the early H/M ratio and the MIBG washout rate.
- Compare MIBG imaging to ECG metrics of sympathetic innervation.
- Examine the relationship between inflammation and regional myocardial innervation and rest myocardial perfusion using quantitative and qualitative SPECT imaging. Specifically, the investigators will aim to determine if inflammation is associated with perfusion/innervation mismatch.
- Keywords
- cardiac, innervation, inflammation, sudden, death
- Medical subject headings
- Cardiomyopathy, Dilated, Inflammation, Death, Sudden, Cardiac, Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Primary Prevention of Sudden Cardiac Death | No intervention will be administered. This is an observational study testing the association of inflammation and cardiac sympathetic innervation using I-123-MIBG gamma scintigraphy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine if inflammation is associated with abnormal cardiac sympathetic innervation in patients enrolled in the PROSE-ICD study.
The investigators will determine if inflammation, measured by high sensitivity C-reactive protein is associated with abnormal cardaic sympathetic innervation defined as a heart to mediastinum ratio < 1.60.
Measured: within 3 years
Secondary outcomes (3)
Determine if inflammation, measured by IL-6, is associated with abnormal cardiac sympathetic innervation, measured by MIBG imaging
The investigators will determine if inflammation, measured by IL-6 is associated with abnormal cardaic sympathetic innervation defined as a heart to mediastinum ratio < 1.60.
Measured: within 3 years
Examine the combination of CRP and MIBG
Examine the combination of C-reactive protein levels and abnormal sympathetic innervation defined as a heart to mediastinum ratio <1.60 to predict appropriate ICD therapies in the PROSE-ICD cohort.
Measured: within 3 years
Compare several MIBG imaging metrics of sympathetic innervation, in addition to the late H/M ratio, including the early H/M ratio and the MIBG washout rate, in regards to their association with biomarkers of inflammation (CRP and IL-6).
Measured: within 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2013 (estimated)
- Study startMar 2012
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic CardiomyopathyStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), General Electric
- Responsible party
- Sponsor
- Investigators
- Richard T George, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01919983
- Sponsor's protocol ID
- 1R21HL106586-1
- Other IDs
- 1R21HL106586
- Status last verified
- Dec 2017
- First submitted
- 6 Aug 2013
- Last updated
- 8 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death
- ClinicalTrials.gov ID
- NCT01919983
- Acronym / sponsor ID
- 1R21HL106586-1
- Keywords
- cardiac, innervation, inflammation, sudden, death
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), General Electric
- Study start
- Mar 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 9 Aug 2013 (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.
Despite pharmacologic advances for the treatment of congestive heart failure (HF), sudden cardiac death (SCD) and pump failure remain the leading causes of mortality in patients with HF. Although, SCD is poorly understood, implantable cardiac defibrillators (ICD) have been shown to be an effective, but costly therapy in preventing SCD. At present, left ventricular systolic dysfunction is our best independent predictor of SCD, but only moderately predicts those patients who will eventually benefit from the placement of an ICD and, in most cases, left ventricular (LV) systolic dysfunction is a non-modifiable risk factor once acquired. As a result, there exists an intensive search for biomarkers that could improve the prediction of SCD and have the potential for risk factor modification.
Experimental and clinical evidence has established that inflammation plays a critical role in stable coronary disease, plaque rupture, acute myocardial infarction, heart failure, and SCD. Studies at our institution have demonstrated that elevated levels of hsCRP and Interleukin-6 are predictive of arrhythmic SCD; however, the mechanism of causing this increased risk is unclear.
Another well-known risk factor for SCD is abnormal sympathetic innervation. The most robust clinical test of sympathetic innervation to date is Iodine-123 Metaiodobenzylguanidine (MIBG) imaging with gamma scintigraphy. MIBG imaging has emerged as one of our strongest predictors of SCD by detecting sympathetic nervous system abnormalities in patients with HF. Preclinical and clinical evidence suggests that myocardial inflammation adversely affects myocardial innervation.
Based on these findings, the investigators hypothesize that elevated levels of inflammatory biomarkers are associated with abnormal sympathetic innervation as measured by MIBG imaging. The investigators aim to establish the strength of this association. This proposal will leverage unique access to the largest, most extensively phenotyped cohort of patients who have undergone ICD implantation for primary prevention of SCD, the PRospective Observational Study of the ICD in SCD, (PROSE-ICD).
Detailed description
The primary aim is as follows:
Primary Aim 1: Determine if inflammation is associated with abnormal cardiac sympathetic innervation in patients enrolled in the PROSE-ICD study.
Rationale/Hypothesis: The investigators hypothesize that patients with increased biomarkers of systemic inflammation have abnormal cardiac sympathetic innervation as measured by MIBG imaging.
Specifically the investigators will: Image 100 patients from the PROSE-ICD cohort, 50 each from the highest and lowest quartiles of hsCRP levels and determine whether patients with biomarker evidence of increased inflammation also have abnormal sympathetic innervation.
In addition, the investigators will pursue the following secondary aims:
- Determine if inflammation, measured by IL-6, is associated with abnormal cardiac sympathetic innervation, measured by MIBG imaging, in patients enrolled in the PROSE-ICD study.
- Examine the association of CRP and MIBG with ICD therapies in PROSE-ICD.
- Compare several MIBG imaging metrics of sympathetic innervation, in addition to the late H/M ratio, including the early H/M ratio and the MIBG washout rate.
- Compare MIBG imaging to ECG metrics of sympathetic innervation.
- Examine the relationship between inflammation and regional myocardial innervation and rest myocardial perfusion using quantitative and qualitative SPECT imaging. Specifically, the investigators will aim to determine if inflammation is associated with perfusion/innervation mismatch.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Primary Prevention of Sudden Cardiac Death | – | –No intervention will be administered. This is an observational study testing the association of inflammation and cardiac sympathetic innervation using I-123-MIBG gamma scintigraphy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a cardiomyopathy with an LVEF ≤35% who have undergone placement of an implantable cardioverter-defibrillator for primary prevention of sudden cardiac death
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Determine if inflammation is associated with abnormal cardiac sympathetic innervation in patients enrolled in the PROSE-ICD study.
Time frame: within 3 years
The investigators will determine if inflammation, measured by high sensitivity C-reactive protein is associated with abnormal cardaic sympathetic innervation defined as a heart to mediastinum ratio < 1.60.
3 secondary outcomes
Determine if inflammation, measured by IL-6, is associated with abnormal cardiac sympathetic innervation, measured by MIBG imaging
Time frame: within 3 years
Examine the combination of CRP and MIBG
Time frame: within 3 years
Compare several MIBG imaging metrics of sympathetic innervation, in addition to the late H/M ratio, including the early H/M ratio and the MIBG washout rate, in regards to their association with biomarkers of inflammation (CRP and IL-6).
Time frame: within 3 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 8 Dec 2017.
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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.
Richard T George, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ischemic Cardiomyopathy and Dilated Cardiomyopathy, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 8 Dec 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 United States. 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.
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?
Determine if inflammation is associated with abnormal cardiac sympathetic innervation in patients enrolled in the PROSE-ICD study. (time frame: within 3 years). 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 8 Dec 2017.