Study Results
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Basic Information
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TERMINATED
PHASE1
42 participants
INTERVENTIONAL
2013-04-24
2018-09-27
Brief Summary
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This aim of the proposal to identify the prevalence of cardiac allograft remodeling on current immunosuppressive strategies and determine risk factors for its development. It will also identify molecular pathways associated with cardiac allograft remodeling and determine the impact of Sirolimus on these pathways.
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Detailed Description
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Cardiac allograft remodeling (CAR), or changes in heart's geometric pattern, is one of the common complications after heart transplantation and often inflicts poor quality of life, heart failure, and decreased survival. The risk factors and mechanism for the development and progression of CAR are poorly defined, and there is no effective treatment for this condition. In the proposed study, we will identify the prevalence, risk factors, and effect of CAR on physical capacity, cardiac vascular disease, and patient survival after a heart transplant. For assessment of heart geometry, we will use cardiac magnetic resonance imaging (CMRI), a techniques used to visualize the internal structures of the body in detail. CMRI is considered as being a "gold standard" for evaluating the heart's structure and function. We will also evaluate the molecular and genetic markers associated with development and progression of CAR after heart transplantation.
The drug Sirolimus, a new anti-rejection agent, can be used in place of calcineurin inhibitors after heart transplantation. Recent experimental and animal studies indicate that Sirolimus can attenuate the changes in the heart's geometry after a transplant (i.e., CAR) and improve heart function. We will assess the effect of Sirolimus on CAR in humans and will evaluate molecular and genetic markers associated with this effect.
It is our goal to provide an important insight into the nature of CAR after heart transplantation and its response to new anti-rejection drug Sirolimus. This information will have a significant impact on the treatment of heart transplant recipients and thus improve quality of life and prolong survival after heart transplantation.
Conditions
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Study Design
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RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Cardiac biopsy C4D stain
A procedure that removes a very small sample of your heart muscle so that it can be evaluated in the lab. This procedure may be done to determine the cause of cardiac myopathy (a weakened heart muscle) or to check for rejection after a heart transplant.
Cardiac Biopsy C4D stain
A long, thin tube called a biopsy catheter is inserted through a vein in your neck or grion and guided through your blood vessels to your heart.
Genetic Mechanism of M-TOR
To identify the molecular and genetic mechanisms associated with development of early post-transplant CAR, and to evaluate the impact of mTOR-inhibitor Sirolimus on this process.
Sirolimus dosage is based on blood levels.
Genetic Mechanism of M-TOR
To identify the molecular and genetic mechanisms associated with development of early post-transplant CAR, and to evaluate the impact of mTOR-inhibitor Sirolimus on this process.
Cardiac MRI
Cardiac Magnetic Resonance Imaging (MRI) produces no side effects from the magnetic fields and radio waves and doesn't carry a risk of cancer or birth defects. Serious reactions to the special contrast dyes used for MRI are very rare. The MRI examination poses almost no risk to the average patient when appropriate safety guidelines are followed, however side effects are possible and include headache, nausea, dizziness, change in taste and allergic reaction. Such reactions usually are mild and easily controlled by medication.
Cardiac MRI
1 month post HTx, year 1 and year 2 annual post HTx eval. CMRIs completed using 1.5-Tesla Whole Body MRI system. Scout images will determine short \& long-axis views of the heart. ECG-gated cine MR of 3 long axis and a contiguous short axis orientation will be obtained. T1-weighted delayed enhancement images will be obtained 10 minutes after injection of a gadolinium-based contrast agent. Measurements from each slice will be summed using the method of disks. Myocardial mass will be estimated by multiplying the myocardial wall volume at end diastole by the specific gravity of muscle (1.05gm/ml) and LV hypertrophy will be defined as LV mass indexed to height in meters 2.7 \>/=35.8 g/m 2.7) (18). Delayed Gadolinium enhancement will be defined as any enhancement pattern greater than 0%.
Coronary Angiography with IVUS
Coronary angiography is a test that uses dye and special x rays to show the insides of your coronary arteries. The coronary arteries supply oxygen-rich blood to your heart.
Intravascular ultrasound is a test that uses sound waves to see inside blood vessels. This article discusses intravascular ultrasound to see inside the coronary arteries, the blood vessels that supply the heart.
Coronary angiography with IVUS
Coronary angiography is a test that uses dye and special x rays to show the insides of your coronary arteries. The coronary arteries supply oxygen-rich blood to your heart.
Intravascular ultrasound is a test that uses sound waves to see inside blood vessels. This article discusses intravascular ultrasound to see inside the coronary arteries, the blood vessels that supply the heart.
Cardiopulmonary Exercise Test (CPET)
Is a highly sensitive, non-invasive stress test. It is considered a stress test because the exercise stresses your body's systems by making them work faster and harder. A disease or condition that affects the heart, lungs or muscles will limit how much faster and harder these systems can work. A CPET assesses how well the heart, lungs, and muscles are working individually, and how these systems are working in unison. Your heart and lungs work together to deliver oxygen to your muscles, where it is used to make energy, and to remove carbon dioxide from your body.
Cardiopulmonary Exercise Test (CPET)
The Cardiopulmonary Exercise Test is a highly sensitive, non-invasive stress test. It is considered a stress test because the exercise stresses your body's systems by making them work faster and harder. A disease or condition that affects the heart, lungs or muscles will limit how much faster and harder these systems can work. A CPET assesses how well the heart, lungs, and muscles are working individually, and how these systems are working in unison. Your heart and lungs work together to deliver oxygen to your muscles, where it is used to make energy, and to remove carbon dioxide from your body.
MTor Immunosuppression
Sirolimus
Sirolimus dosage is based on blood levels.
To assess the potential of mTOR immunosuppressant Sirolimus in attenuation of CAR in HTx recipients and therefore, improve pre-existing cardiac allograft function, vasculopathy, and exercise capacity.
Cardiac MRI
1 month post HTx, year 1 and year 2 annual post HTx eval. CMRIs completed using 1.5-Tesla Whole Body MRI system. Scout images will determine short \& long-axis views of the heart. ECG-gated cine MR of 3 long axis and a contiguous short axis orientation will be obtained. T1-weighted delayed enhancement images will be obtained 10 minutes after injection of a gadolinium-based contrast agent. Measurements from each slice will be summed using the method of disks. Myocardial mass will be estimated by multiplying the myocardial wall volume at end diastole by the specific gravity of muscle (1.05gm/ml) and LV hypertrophy will be defined as LV mass indexed to height in meters 2.7 \>/=35.8 g/m 2.7) (18). Delayed Gadolinium enhancement will be defined as any enhancement pattern greater than 0%.
Coronary angiography with IVUS
Coronary angiography is a test that uses dye and special x rays to show the insides of your coronary arteries. The coronary arteries supply oxygen-rich blood to your heart.
Intravascular ultrasound is a test that uses sound waves to see inside blood vessels. This article discusses intravascular ultrasound to see inside the coronary arteries, the blood vessels that supply the heart.
Cardiac Allograft Remodeling
A surgical procedure in which a diseased heart is replaced with a healthy heart from a deceased person.
M-TOR Immunosuppression
Sirolimus (INN/USAN), also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. It prevents activation of T cells and B-cells by inhibiting their response to interleukin-2 (IL-2).
Sirolimus dosage based on blood levels.
Cardiac Allograft Remodeling
A surgical procedure in wich a diseased heart is replaced with a healthy heart from a deceased person.
Cardiac Allograft Remodeling
A surgical procedure in which a diseased heart is replaced with a healthy heart from a deceased person.
Interventions
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Cardiac MRI
1 month post HTx, year 1 and year 2 annual post HTx eval. CMRIs completed using 1.5-Tesla Whole Body MRI system. Scout images will determine short \& long-axis views of the heart. ECG-gated cine MR of 3 long axis and a contiguous short axis orientation will be obtained. T1-weighted delayed enhancement images will be obtained 10 minutes after injection of a gadolinium-based contrast agent. Measurements from each slice will be summed using the method of disks. Myocardial mass will be estimated by multiplying the myocardial wall volume at end diastole by the specific gravity of muscle (1.05gm/ml) and LV hypertrophy will be defined as LV mass indexed to height in meters 2.7 \>/=35.8 g/m 2.7) (18). Delayed Gadolinium enhancement will be defined as any enhancement pattern greater than 0%.
Coronary angiography with IVUS
Coronary angiography is a test that uses dye and special x rays to show the insides of your coronary arteries. The coronary arteries supply oxygen-rich blood to your heart.
Intravascular ultrasound is a test that uses sound waves to see inside blood vessels. This article discusses intravascular ultrasound to see inside the coronary arteries, the blood vessels that supply the heart.
Cardiac Allograft Remodeling
A surgical procedure in which a diseased heart is replaced with a healthy heart from a deceased person.
M-TOR Immunosuppression
Sirolimus (INN/USAN), also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. It prevents activation of T cells and B-cells by inhibiting their response to interleukin-2 (IL-2).
Sirolimus dosage based on blood levels.
Cardiac Biopsy C4D stain
A long, thin tube called a biopsy catheter is inserted through a vein in your neck or grion and guided through your blood vessels to your heart.
Genetic Mechanism of M-TOR
To identify the molecular and genetic mechanisms associated with development of early post-transplant CAR, and to evaluate the impact of mTOR-inhibitor Sirolimus on this process.
Cardiopulmonary Exercise Test (CPET)
The Cardiopulmonary Exercise Test is a highly sensitive, non-invasive stress test. It is considered a stress test because the exercise stresses your body's systems by making them work faster and harder. A disease or condition that affects the heart, lungs or muscles will limit how much faster and harder these systems can work. A CPET assesses how well the heart, lungs, and muscles are working individually, and how these systems are working in unison. Your heart and lungs work together to deliver oxygen to your muscles, where it is used to make energy, and to remove carbon dioxide from your body.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
19 Years
70 Years
ALL
No
Sponsors
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University of Nebraska
OTHER
Responsible Party
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Principal Investigators
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Brian Lowes, MD
Role: PRINCIPAL_INVESTIGATOR
University of Nebraska
Locations
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University of Nebraska Medical Center
Omaha, Nebraska, United States
Countries
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References
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
0339-12-FB
Identifier Type: -
Identifier Source: org_study_id
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