Clinical Trials Logo

Clinical 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 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.


Clinical Trial 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


Related Conditions & MeSH terms


NCT number NCT01889992
Study type Interventional
Source University of Nebraska
Contact
Status Terminated
Phase Phase 1
Start date April 24, 2013
Completion date September 27, 2018

See also
  Status Clinical Trial Phase
Recruiting NCT05060991 - Impact of Immunosuppression Adjustment on COVID-19 Vaccination Response in Kidney Transplant Recipients Phase 4
Completed NCT02833805 - NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia Phase 2
Completed NCT01252537 - Immunosuppression in HIV-infected Patients With Tuberculosis in Ethiopia N/A
Completed NCT00621699 - Pharmacokinetic Drug Interaction Between Ezetimibe and Tacrolimus After Single Dose Administration in Healthy Subjects Phase 1
Completed NCT01678937 - Immune Tolerance and Alloreactivity in Liver Transplant Recipients on Different Monotherapy Immunosuppressive Agents N/A
Completed NCT00788021 - Protective Immunity Project 01 N/A
Active, not recruiting NCT00166842 - Sirolimus Blood Concentrations on Conversion From Oral Solution to Tablets Phase 4
Recruiting NCT05616130 - Pathological Myeloid Activation After Sepsis and Trauma
Completed NCT03117192 - Zinc Supplementation on Cellular Immunity in Thalassemia Major Phase 4
Recruiting NCT01568697 - Oral Bacteria and Immune System Problems Involved in Gum Disease (Periodontitis)
Not yet recruiting NCT06024226 - Role of MDSCs and Cancer Stem Cells and Their Cross Talks in NSCLC
Not yet recruiting NCT04961229 - Booster Dose of COVID-19 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response Phase 4
Completed NCT03139565 - High Dose vs. Standard Influenza Vaccine in Adult SOT Phase 3
Completed NCT02547753 - Dental Extractions Among Renal Transplant Recipients
Completed NCT01702207 - Evaluation Of Switching From Twice Daily Tacrolimus To Once Daily Formulation On Cardiovascular Risk Phase 4
Completed NCT00626808 - A Post Marketing Evaluation of the Effectiveness of FluMist Risk Minimization Plan in Children Phase 4
Completed NCT00419575 - Renal Transplantation With Immune Monitoring N/A
Completed NCT00783380 - Influenza Vaccination in Immunocompromized Patients Phase 4
Completed NCT04835948 - Efficacy of Single Dose Anti-thymocyte Globulin in the Modulation of T Lymphocytes in Kidney Transplantation
Recruiting NCT05043870 - Combined Immunosuppression for Pediatric Crohn's Disease Phase 4