Cardiac HypertrophyPhase 1CARNCT01889992
Cardiac Allograft Remodeling and Effects of Sirolimus
A Phase 1 study testing Cardiac MRI, Coronary angiography with IVUS and Cardiac Allograft Remodeling in people with Cardiac Hypertrophy and Immunosuppression, run by University of Nebraska at 1 site in United States.
Trial summary
Cardiac allograft remodeling causes poor quality of life, allograft failure and increased mortality after heart transplantation. Risk factors for cardiac allograft remodeling and its progression are poorly defined and there is a need for effective interventions.This is a multi-factorial phenomenon, associated with… Read more about this study
- Who is it for?
- Ages 19 to 70 years
- Conditions the study is for
- Cardiac Hypertrophy, Immunosuppression
- What is being tested?
- Cardiac MRI, Coronary angiography with IVUS and Cardiac Allograft Remodeling
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Apr 2013to 27 Sep 2018
- Phase
- 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 19 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All adult cardiac transplant recipients undergoing heart transplantation at UNMC/TNMC.
Who cannot join
- Adult cardiac transplant recipients with acute rejection (ISHLT R> grade 2) or acute infection.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Cardiac Allograft Remodeling and Effects of Sirolimus on Its Progression
Cardiac allograft remodeling causes poor quality of life, allograft failure and increased mortality after heart transplantation. Risk factors for cardiac allograft remodeling and its progression are poorly defined and there is a need for effective interventions.This is a multi-factorial phenomenon, associated with various immunological and non-immunological factors. Animal studies suggest M-TOR inhibition attenuates cardiac allograft remodeling secondary to down-regulation of M-TOR downstream targets and increased autophagy. There is a paucity of data regarding effect of Sirolimus, a M-TOR inhibitor, on human heart remodeling.
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.
Read the detailed description
Heart transplantation has become a well-established treatment option for patients with end-stage heart disease and currently has a one-year survival rate of 90%, a five-year survival rate of 70%, and 10-year survival rate of 50%. The introduction of anti-rejection treatment thirty years ago with drugs known as calcineurin inhibitors have resulted in a significant improvement in the survival of heart transplant recipients. However, most of this improvement occurs during the first year after transplantation. Beyond the first year, the mortality rate of heart transplant recipients has not changed, which indicates that the causes of late complications have not been affected in the last three decades by improvements in post-transplant care. It becomes apparent that in order to improve the late outcomes, the focus in heart transplant research needs to be shifted to the prevention and the treatment of late complications.
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
- Cardiac Hypertrophy, Immunosuppression
- Being tested
- Cardiac MRI, Coronary angiography with IVUS, Cardiac Allograft Remodeling, M-TOR Immunosuppression, Cardiac Biopsy C4D stain
- Keywords
- Heart transplantation, Cardiac allograft remodeling, Immunosuppression, Cardiac MRI, M-TOR inhibitor
- Medical subject headings
- Cardiomegaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac MRIRadiation
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 IVUSProcedure or surgery
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 RemodelingOther
Also called heart hypertrophy
A surgical procedure in which a diseased heart is replaced with a healthy heart from a deceased person.
M-TOR ImmunosuppressionDrug
Also called Sirolimus
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 stainProcedure or surgery
Also called heart biopsy
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-TORGenetic
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)Other
Also called Stress test
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.
| Study group | Role | What they receive |
|---|---|---|
| Cardiac biopsy C4D stain | Active comparator | 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. Receives: Procedure: Cardiac Biopsy C4D stain |
| Genetic Mechanism of M-TOR | Experimental | 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. Receives: Genetic: Genetic Mechanism of M-TOR |
| Cardiac MRI | Active comparator | 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. Receives: Radiation: Cardiac MRI |
| Coronary Angiography with IVUS | Active comparator | 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. Receives: Procedure: Coronary angiography with IVUS |
| Cardiopulmonary Exercise Test (CPET) | Active comparator | 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. Receives: Other: Cardiopulmonary Exercise Test (CPET) |
| MTor Immunosuppression | Experimental | 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. Receives: Radiation: Cardiac MRI; Procedure: Coronary angiography with IVUS; Other: Cardiac Allograft Remodeling; Drug: M-TOR Immunosuppression |
| Cardiac Allograft Remodeling | Experimental | A surgical procedure in wich a diseased heart is replaced with a healthy heart from a deceased person. Receives: Other: Cardiac Allograft Remodeling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment in left ventricular hypertrophy
The primary end point will be the change from baseline in LV mass indexed to height in meters 2.7 and LV concentricity as assessed by MRI during 12 months of the treatment.
Measured: One year
Secondary outcomes (2)
Assess outcomes
The secondary end points will be changes from baseline in LV function.
Measured: One year
Access outcomes
Exercise performance (peak VO2, equivalent for carbon dioxide (VE/VCO2)and coronary vessel intimal thickening.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2013 (estimated)
- Study start24 Apr 2013
- Primary completion27 Sep 2018
- Study completion27 Sep 2018
Why it stopped: PI left University and project not continued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (110)Papers the sponsor has linked to this study.
- Other trials for Cardiac HypertrophyStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brian Lowes, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01889992
- Sponsor's protocol ID
- 0339-12-FB
- Acronym
- CAR
- Status last verified
- Aug 2023
- First submitted
- 19 Jun 2013
- Last updated
- 30 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Grossman E, Messerli FH. Hypertension and diabetes. Adv Cardiol. 2008;45:82-106. doi: 10.1159/000115189.
PubMed 18230957Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990 May 31;322(22):1561-6. doi: 10.1056/NEJM199005313222203.
PubMed 2139921Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991 Mar 1;114(5):345-52. doi: 10.7326/0003-4819-114-5-345.
PubMed 1825164Esposito G, Rapacciuolo A, Naga Prasad SV, Rockman HA. Cardiac hypertrophy: role of G protein-coupled receptors. J Card Fail. 2002 Dec;8(6 Suppl):S409-14. doi: 10.1054/jcaf.2002.129283.
PubMed 12555153Goodroe R, Bonnema DD, Lunsford S, Anderson P, Ryan-Baille B, Uber W, Ikonomidis J, Crumbley AJ, VanBakel A, Zile MR, Pereira N. Severe left ventricular hypertrophy 1 year after transplant predicts mortality in cardiac transplant recipients. J Heart Lung Transplant. 2007 Feb;26(2):145-51. doi: 10.1016/j.healun.2006.11.003.
PubMed 17258148Tischler MD, Lee RT, Plappert T, Mudge GH, St John Sutton M, Parker JD. Serial assessment of left ventricular function and mass after orthotopic heart transplantation: a 4-year longitudinal study. J Am Coll Cardiol. 1992 Jan;19(1):60-6. doi: 10.1016/0735-1097(92)90052-o.
PubMed 1729347Vigneswaran WT, Rumberger JA, Rodeheffer RJ, Breen JF, McGregor CG. Ventricular remodeling after orthotopic cardiac transplantation. Mayo Clin Proc. 1996 Aug;71(8):735-42. doi: 10.4065/71.8.735.
PubMed 8691893Raichlin E, Villarraga HR, Chandrasekaran K, Clavell AL, Frantz RP, Kushwaha SS, Rodeheffer RJ, McGregor CG, Daly RC, Park SJ, Kremers WK, Edwards BS, Pereira NL. Cardiac allograft remodeling after heart transplantation is associated with increased graft vasculopathy and mortality. Am J Transplant. 2009 Jan;9(1):132-9. doi: 10.1111/j.1600-6143.2008.02474.x. Epub 2008 Nov 27.
PubMed 19067662Hosenpud JD, Norman DJ, Cobanoglu MA, Floten HS, Conner RM, Starr A. Serial echocardiographic findings early after heart transplantation: evidence for reversible right ventricular dysfunction and myocardial edema. J Heart Transplant. 1987 Nov-Dec;6(6):343-7.
PubMed 2961856Raichlin E, Al-Omari MA, Hayes CL, Edwards BS, Frantz RP, Boilson BA, Clavell AL, Rodeheffer RJ, Schirger JA, Kushwaha SS, Allison TG, Pereira NL. Cardiac allograft hypertrophy is associated with impaired exercise tolerance after heart transplantation. J Heart Lung Transplant. 2011 Oct;30(10):1153-60. doi: 10.1016/j.healun.2011.04.012. Epub 2011 May 31.
PubMed 21621424Doggrell SA. Is everolimus useful in preventing allograft rejection and vasculopathy after heart transplant? Expert Opin Investig Drugs. 2004 Feb;13(2):161-3. doi: 10.1517/13543784.13.2.161.
PubMed 14996650Mancini D, Pinney S, Burkhoff D, LaManca J, Itescu S, Burke E, Edwards N, Oz M, Marks AR. Use of rapamycin slows progression of cardiac transplantation vasculopathy. Circulation. 2003 Jul 8;108(1):48-53. doi: 10.1161/01.CIR.0000070421.38604.2B. Epub 2003 May 12.
PubMed 12742978Raichlin E, Bae JH, Khalpey Z, Edwards BS, Kremers WK, Clavell AL, Rodeheffer RJ, Frantz RP, Rihal C, Lerman A, Kushwaha SS. Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. Circulation. 2007 Dec 4;116(23):2726-33. doi: 10.1161/CIRCULATIONAHA.107.692996. Epub 2007 Nov 19.
PubMed 18025531Raichlin E, Edwards BS, Kremers WK, Clavell AL, Rodeheffer RJ, Frantz RP, Pereira NL, Daly RC, McGregor CG, Lerman A, Kushwaha SS. Acute cellular rejection and the subsequent development of allograft vasculopathy after cardiac transplantation. J Heart Lung Transplant. 2009 Apr;28(4):320-7. doi: 10.1016/j.healun.2009.01.006.
PubMed 19332257Patel PC, Reimold SC, Araj FG, Ayers CR, Kaiser PA, Peshock RM, Yancy CW, Ring WS, Gupta S, Mishkin JD, Mammen PP, Markham DW, Drazner MH. Concentric left ventricular hypertrophy as assessed by cardiac magnetic resonance imaging and risk of death in cardiac transplant recipients. J Heart Lung Transplant. 2010 Dec;29(12):1369-79. doi: 10.1016/j.healun.2010.05.008.
PubMed 20599402
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Allograft Remodeling and Effects of Sirolimus on Its Progression
- ClinicalTrials.gov ID
- NCT01889992
- Acronym / sponsor ID
- CAR / 0339-12-FB
- Conditions
- Cardiac Hypertrophy, Immunosuppression
- Keywords
- Heart transplantation, Cardiac allograft remodeling, Immunosuppression, Cardiac MRI, M-TOR inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left University and project not continued
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 24 Apr 2013 (actual)
- Primary completion
- 27 Sep 2018 (actual)
- Study completion
- 27 Sep 2018 (actual)
- First posted
- 1 Jul 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.
Cardiac allograft remodeling causes poor quality of life, allograft failure and increased mortality after heart transplantation. Risk factors for cardiac allograft remodeling and its progression are poorly defined and there is a need for effective interventions.This is a multi-factorial phenomenon, associated with various immunological and non-immunological factors. Animal studies suggest M-TOR inhibition attenuates cardiac allograft remodeling secondary to down-regulation of M-TOR downstream targets and increased autophagy. There is a paucity of data regarding effect of Sirolimus, a M-TOR inhibitor, on human heart remodeling.
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.
Detailed description
Heart transplantation has become a well-established treatment option for patients with end-stage heart disease and currently has a one-year survival rate of 90%, a five-year survival rate of 70%, and 10-year survival rate of 50%. The introduction of anti-rejection treatment thirty years ago with drugs known as calcineurin inhibitors have resulted in a significant improvement in the survival of heart transplant recipients. However, most of this improvement occurs during the first year after transplantation. Beyond the first year, the mortality rate of heart transplant recipients has not changed, which indicates that the causes of late complications have not been affected in the last three decades by improvements in post-transplant care. It becomes apparent that in order to improve the late outcomes, the focus in heart transplant research needs to be shifted to the prevention and the treatment of late complications.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cardiac biopsy C4D stain | Active comparator | Procedure: Cardiac Biopsy C4D stainA 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. |
| Genetic Mechanism of M-TOR | Experimental | Genetic: Genetic Mechanism of M-TORTo 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. |
| Cardiac MRI | Active comparator | Radiation: Cardiac MRICardiac 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. |
| Coronary Angiography with IVUS | Active comparator | Procedure: Coronary angiography with IVUSCoronary 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) | Active comparator | Other: 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. |
| MTor Immunosuppression | Experimental | Radiation: Cardiac MRI, Procedure: Coronary angiography with IVUS, Other: Cardiac Allograft Remodeling, Drug: M-TOR ImmunosuppressionSirolimus 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 Allograft Remodeling | Experimental | Other: Cardiac Allograft RemodelingA surgical procedure in wich a diseased heart is replaced with a healthy heart from a deceased person. |
Who may qualify
- Ages
- 19 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All adult cardiac transplant recipients undergoing heart transplantation at UNMC/TNMC.
Key exclusion criteria (1 listed)
- Adult cardiac transplant recipients with acute rejection (ISHLT R> grade 2) or acute infection.
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 |
|---|---|---|
| Cardiac MRI1 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%. | Radiation | Cardiac MRI, MTor Immunosuppression |
| Coronary angiography with IVUSCoronary 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. | Procedure or surgery | Coronary Angiography with IVUS, MTor Immunosuppression |
| Cardiac Allograft RemodelingAlso: heart hypertrophyA surgical procedure in which a diseased heart is replaced with a healthy heart from a deceased person. | Other | Cardiac Allograft Remodeling, MTor Immunosuppression |
| M-TOR ImmunosuppressionAlso: SirolimusSirolimus (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. | Drug | MTor Immunosuppression |
| Cardiac Biopsy C4D stainAlso: heart biopsyA 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. | Procedure or surgery | Cardiac biopsy C4D stain |
| Genetic Mechanism of M-TORTo 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. | Genetic | Genetic Mechanism of M-TOR |
| Cardiopulmonary Exercise Test (CPET)Also: Stress testThe 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 | Cardiopulmonary Exercise Test (CPET) |
Primary outcome
Assessment in left ventricular hypertrophy
Time frame: One year
The primary end point will be the change from baseline in LV mass indexed to height in meters 2.7 and LV concentricity as assessed by MRI during 12 months of the treatment.
2 secondary outcomes
Assess outcomes
Time frame: One year
Access outcomes
Time frame: One year
Results and safety
The study was stopped early (reason given: PI left University and project not continued). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Results publication: PubMed 18230957Grossman E, Messerli FH. Hypertension and diabetes. Adv Cardiol. 2008;45:82-106. doi: 10.1159/000115189.
- Results publication: PubMed 2139921Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990 May 31;322(22):1561-6. doi: 10.1056/NEJM199005313222203.
- Results publication: PubMed 1825164Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991 Mar 1;114(5):345-52. doi: 10.7326/0003-4819-114-5-345.
- Results publication: PubMed 12555153Esposito G, Rapacciuolo A, Naga Prasad SV, Rockman HA. Cardiac hypertrophy: role of G protein-coupled receptors. J Card Fail. 2002 Dec;8(6 Suppl):S409-14. doi: 10.1054/jcaf.2002.129283.
- Results publication: PubMed 17258148Goodroe R, Bonnema DD, Lunsford S, Anderson P, Ryan-Baille B, Uber W, Ikonomidis J, Crumbley AJ, VanBakel A, Zile MR, Pereira N. Severe left ventricular hypertrophy 1 year after transplant predicts mortality in cardiac transplant recipients. J Heart Lung Transplant. 2007 Feb;26(2):145-51. doi: 10.1016/j.healun.2006.11.003.
- Results publication: PubMed 1729347Tischler MD, Lee RT, Plappert T, Mudge GH, St John Sutton M, Parker JD. Serial assessment of left ventricular function and mass after orthotopic heart transplantation: a 4-year longitudinal study. J Am Coll Cardiol. 1992 Jan;19(1):60-6. doi: 10.1016/0735-1097(92)90052-o.
- Results publication: PubMed 8691893Vigneswaran WT, Rumberger JA, Rodeheffer RJ, Breen JF, McGregor CG. Ventricular remodeling after orthotopic cardiac transplantation. Mayo Clin Proc. 1996 Aug;71(8):735-42. doi: 10.4065/71.8.735.
- Results publication: PubMed 19067662Raichlin E, Villarraga HR, Chandrasekaran K, Clavell AL, Frantz RP, Kushwaha SS, Rodeheffer RJ, McGregor CG, Daly RC, Park SJ, Kremers WK, Edwards BS, Pereira NL. Cardiac allograft remodeling after heart transplantation is associated with increased graft vasculopathy and mortality. Am J Transplant. 2009 Jan;9(1):132-9. doi: 10.1111/j.1600-6143.2008.02474.x. Epub 2008 Nov 27.
- Results publication: PubMed 2961856Hosenpud JD, Norman DJ, Cobanoglu MA, Floten HS, Conner RM, Starr A. Serial echocardiographic findings early after heart transplantation: evidence for reversible right ventricular dysfunction and myocardial edema. J Heart Transplant. 1987 Nov-Dec;6(6):343-7.
- Results publication: PubMed 21621424Raichlin E, Al-Omari MA, Hayes CL, Edwards BS, Frantz RP, Boilson BA, Clavell AL, Rodeheffer RJ, Schirger JA, Kushwaha SS, Allison TG, Pereira NL. Cardiac allograft hypertrophy is associated with impaired exercise tolerance after heart transplantation. J Heart Lung Transplant. 2011 Oct;30(10):1153-60. doi: 10.1016/j.healun.2011.04.012. Epub 2011 May 31.
- Results publication: PubMed 14996650Doggrell SA. Is everolimus useful in preventing allograft rejection and vasculopathy after heart transplant? Expert Opin Investig Drugs. 2004 Feb;13(2):161-3. doi: 10.1517/13543784.13.2.161.
- Results publication: PubMed 12742978Mancini D, Pinney S, Burkhoff D, LaManca J, Itescu S, Burke E, Edwards N, Oz M, Marks AR. Use of rapamycin slows progression of cardiac transplantation vasculopathy. Circulation. 2003 Jul 8;108(1):48-53. doi: 10.1161/01.CIR.0000070421.38604.2B. Epub 2003 May 12.
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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.
Brian Lowes, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cardiac MRI, Coronary angiography with IVUS and Cardiac Allograft Remodeling in people with Cardiac Hypertrophy and Immunosuppression, run by University of Nebraska 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?
The sponsor lists 1 inclusion and 1 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: stopped early, as of the sponsor's last update on 30 Aug 2023. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: PI left University and project not continued). Results are not available in the source record.
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?
Assessment in left ventricular hypertrophy (time frame: One year). 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 NCT01889992, which also lists 110 linked publications.
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 30 Aug 2023.