33 Clinical Trials for Various Conditions
This study aims to discover circulating microRNAs (associated with drug doses and levels) that can be used to characterize the overall immune state in pediatric heart transplant patients and predict patients that will go on to develop infection and rejection. MicroRNAs (miRs) are small, non-coding RNA molecules that regulate gene expression and serve as molecular biomarkers found in the circulation.
Immunosuppressive therapy is required to prevent organ rejection, however, dosing of immunosuppressive agents is complicated by patient-specific differences impacting the body's absorption and elimination of these agents. The goal of this research proposal is to clinically validate an innovative precision medicine strategy for dosing the immunosuppressant tacrolimus in pediatric heart transplant, which will in turn lead to improvements in long-term transplant survival outcomes. The strategy and techniques used in this project can be extended to improve drug therapy across multiple pediatric diseases requiring chronic therapy.
The TEAMMATE Trial will enroll 210 pediatric heart transplant patients from 25 centers at 6 months post-transplant and follow each patient for 2.5 years. Half of the participants will receive everolimus and low-dose tacrolimus and the other half will receive tacrolimus and mycophenolate mofetil. The trial will determine which treatment is better at reducing the cumulative risk of coronary artery vasculopathy, chronic kidney disease and biopsy proven-acute cellular rejection without an increase in graft loss due to all causes (e.g. infection, PTLD, antibody mediated rejection).
Heart transplantation is a life-sustaining therapy that allows patients with either congenital or acquired heart disease and severe cardiac dysfunction to survive. Over time, however, the transplanted heart can develop problems. One of the more common and troubling problems is the development of stenoses, or narrowings, within the coronary arteries. These narrowings, technically referred to as coronary artery vasculopathy (CAV for short), account for the single most common cause of death or need for repeat heart transplant in persons more than one year post-transplant. Traditionally, CAV has been diagnosed at cardiac catheterization using coronary angiography (where dye is directly injected into the coronary blood vessels and viewed using special x-ray equipment called fluoroscopy). There is no good treatment for CAV aside from treatment of symptoms and listing for repeat heart transplantation. The goal of this study is to test several newer methods of diagnosing CAV. The first is called coronary flow reserve (catheterization test). The second is called Endo-PAT (a finger probe test) and the third is called contrast-enhanced cardiac MRI (MRI test, only for patients 12 and older). The older method (coronary angiography) will still be used in all cases, in addition to the new tests The goal is, one day, to be able to diagnose patients with CAV earlier in the course, prior to a patient's development of abnormal angiograms. If this can be done, it is possible that better therapies will be able to be used to stop or even reverse the development of CAV, perhaps reducing, or at least delaying, the need for repeat heart transplantation.
Pediatric heart transplant patients have a high-risk cardiovascular profile affecting their long-term outcomes and survival. Currently, no effective cardiovascular preventative care is provided for this pediatric population, in part, due to the fact that clinic-based programs are not easily accessible to children and their families. However, tele-health has been show to improve medical outcomes by making care more accessible to these patients. This study aims to meet the urgent need for an effective and sustainable delivery of preventative care to pediatric heart transplant patients using a diet and exercise intervention program delivered live over the internet direct to these patients' homes.
The purpose of this pilot trial, Transitioning to Adult Care (TRANSIT), is to develop and test an intervention (i.e., a standardized, tailored transition program focused on enhancing adherence) to improve outcomes for emerging adults who underwent heart transplantation as children and transfer to adult care.
Transplant coronary artery disease (TCAD) is a significant cause of morbidity and mortality in pediatric heart transplantation (PHT). Understanding the pathophysiology and early detection along with attempted medical management are crucial in preventing advancement of the disease and retransplantation or mortality. Coronary angiogram, although routinely used is insensitive to detect early TCAD. Measurement of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR) using a doppler pressure and flow intracoronary wire may be more sensitive in evaluating the integrity of coronary vasculature and thus detect pre clinical TCAD. To the best of the investigators knowledge, measurement of these parameters has not been previously reported in PHT.
This open label study will assess the pharmacokinetics and the safety and tolerability of Valcyte (valganciclovir) powder for oral solution in neonatal and infant heart transplant patients \< 4 months of age.
The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients.
The restoration of normal blood flow following a period of ischemia may result in ischemia / reperfusion injury (I/RI), which is characterized by inflammation and oxidative damage to tissues. Varying degrees of I/RI occur upon reperfusion of a donor heart after cold storage. Medications containing antibodies against immune cells have been used for many years as powerful immunosuppressants. These medications, called polyclonal antibody preparations, are generally only used immediately following transplantation and/or to treat rejection. At our institution, one such antibody preparation (Thymoglobulin) is used in most pediatric heart transplant recipients for 3-5 days immediately after transplantation. Because standard immunosuppressive medications (called calcineurin inhibitors) are toxic to the kidneys, the use of Thymoglobulin allows us to delay the initiation of calcineurin inhibitors until the kidneys of completely recovered from the shock of the transplant surgery. We hypothesize that Thymoglobulin may be beneficial in reducing the damage caused by I/RI. Thus, the present study seeks to evaluate the effectiveness of an intra-operative dose of Thymoglobulin (in addition to the standard doses post-operatively) at reducing the effects of I/RI. The study will be a double-bind placebo-controlled trial involving 20 subjects. Biologic markers for I/RI will be assessed at periodic intervals for six months post-transplantation. Subjects receiving intra-operative doses of Thymoglobulin will be compared to the controls in order to assess the effectiveness of intra-operative Thymoglobulin in ameliorating the effects of I/RI.
The purpose of this study is to examine the outcomes of those who have received Daclizumab as part of their immuno-suppression protocol following heart transplantation. Literature suggests that the time to first rejection episode can be avoided or delayed by using induction therapy.
Transplantation is the preferred method of treating many forms of end-stage organ failure. While short-term results have improved, long-term outcomes remain inadequate. Myocardial fibrosis could potentially have an adverse effect on long-term cardiac function. We wish to study the degree of fibrosis to see if we can predict survival following pediatric heart transplantation.
This protocol is designed to obtain information on the drug levels, metabolism, and safety of daclizumab (Zenapax(R)) in children and adolescents undergoing cardiac transplantation. In addition to the drug safety and metabolism information, the number and severity of rejection episodes in patients undergoing cardiac transplantation using the standard immunosuppressive drugs plus daclizumab will be compared with patients who have previously undergone cardiac transplantation at the Baylor College of Medicine and received the same standard immunosuppressive drugs without daclizumab.
The skin disease found in pediatric heart transplant patients represents an atopic dermatitis-like rash that is refractory to systemic immunomodulation.
The survival of children who have received heart transplants has greatly improved over the last ten years. One reason for this is better control over rejection. Rejection medications require a delicate balance of enough medicine to work without causing side effects. It is a goal to avoid both rejection and side effects from the anti-rejection medicines. Usually several medicines are used together to prevent rejection. One of these medicines is often Mycophenolic Acid or CellceptThis medicine has been used longer for adults than is has for children. More information is needed on using it for children. The dose is usually determined by the patient's weight or body surface area. There have been some early studies of the use of Cellcept, but none have proven a relationship between the blood level of the drug and how well it works. More also needs to be known about how this drug works with other anti-rejection drugs and how it works in boys and girls. This study will look more closely at proper dosing, how Cellcept works with other anti-rejection medications, side effects, and any differences in how this medicine works in boys and girls. All patients in the study will be receiving Cellcept and have blood levels of the drug drawn. Results of their usual treatment and testing will be recorded and evaluated for signs of rejection. All the information will be analyzed. Results of this study will be reported to transplant committees locally and nationally.
The investigators hypothesize that injecting donor bone marrow cells into the recipient thymus gland at the time of heart transplantation in children will prove to be feasible and safe. They further hypothesize that recipients receiving donor bone marrow will experience less acute rejection events with reduced long-term requirements for immunosuppressive medications when compared to controls who do not receive marrow but who are managed under an identical immunosuppressive protocol.
The purpose of this study is to collect and compare information on how and when adolescent heart transplant recipients take their prescribed medication. The investigators want to find out if regular use of 'an app' on cell phones, called the Teen Pocket PATH® (TPP), can help adolescents take their medication according to their prescribed dosing schedule. This may then help reduce complications of transplant, such as rejection. The investigators also want to find out if how adolescent heart transplant recipients take their medications affects the development of antibodies in their blood. Antibodies are small proteins in the blood that may develop after heart transplantation, and which can sometimes damage a new heart.
This is a multi-center, prospective, single cohort, observational study of pediatric heart transplant recipients designed to determine the impact of preformed versus de novo human leukocyte antigen (HLA) donor-specific antibodies (DSA), and antibodies to the self-antigens cardiac myosin and vimentin, on chronic allograft function. In addition, the investigators will explore mechanisms of action and predictors of DSA, rejection and altered pathophysiology.
The purpose of this study is to determine the significance of an elevated quantitative EBV PCR and to determine the relationship between a EBV PCR value and the risk of developing PTLD.
We will conduct a two-group randomized controlled trial to examine the eMocha DOT intervention with pediatric HT recipients.In this population, medication nonadherence remains a primary cause of late acute rejection (LAR) episodes, increased number of hospitalizations, graft failure, and patient mortality. Herein, we propose an innovative approach to promote medication adherence and improve patient and graft outcomes.
Heart transplants save the lives of nearly 500 children in heart failure per year. Columbia is one of the largest pediatric heart transplant centers in the world, averaging 25 transplants per year, and providing ongoing care to nearly 250 children with transplanted hearts. After transplant, children are at increased risk to develop sudden onset of abnormally fast heart rates. This research project will study adenosine, a medication that is routinely used to slow fast heart rates in non-transplanted children (i.e. normal hearts), and its effects on the transplanted heart. Adenosine is often not used in patients with transplanted hearts because, based on prior limited research in adult patients, the standard adult dose may have a longer medication effect, producing a slower heart rate for an undesirable period of time. However, the current alternatives to adenosine treatment are either inappropriate for the pediatric age range, or have increased risk of unwanted side effects. This research project will answer two questions: is adenosine safe to give a child who has had a heart transplant, and will it be effective in treating the fast heart rate? All pediatric heart transplant patients undergo regular heart testing, known as a cardiac catheterization, one or more times per year. Three days before testing, participants will be asked to stop a regular medication, dipyridamole, because it slows the breakdown of adenosine in the body, and may increase its effects. (Of note, all patients that are on dipyridamole are also on aspirin, which gives a second line of heart protection, and will not be stopped.) After regular cardiac catheterization, all patients will already have intravenous (IV) access to give medication. Also, this setting allows the opportunity to have a back-up pacing catheter in the heart, ensuring that there will not be a longer than desired effect from the medication. Adenosine will be given per a low-dose protocol until either the medication effect is seen or the maximum dose is reached. There will be no difference in procedure recovery period time, and patients will resume regular home medications after finishing the test. As Columbia is one of largest pediatric heart transplant centers in the world, studying the effects of adenosine at low doses will benefit the investigators population greatly, either to find a new recommended medication dose, or to provide evidence that this medication is truly inadvisable for the investigators patients. The initial study was completed with all 80 patients enrolled and tested. Subsequent testing is now ongoing on patients in whom dipyridamole was stopped prior to their initial testing with a repeat study without discontinuing the dipyridamole. We anticipate re-testing about 30 of the 80 patients.
The long-term goal of this research initiative is to develop a new valve replacement option for neonates, infants and young children. The central hypothesis is that transplantation of a freshly isolated heart valve will be associated with superior outcomes compared to currently available options, including preserved cadaver valves, bioprosthetic tissue valves, or mechanical valves. This new operation has been named "partial heart transplantation". The proposed study is a single-center, nonrandomized single arm pilot trial of "partial heart transplantation" in neonates, infants and young children who require semilunar heart valve replacement. This "first in man" trial seeks to determine whether valve replacement using partial heart transplant is feasible and safe. Primary aims are survival one year and five years following the procedure. The hypothesis is that, when compared to historical controls who have undergone homograft valve replacement, those undergoing partial heart transplantation will have equal or superior survival one year and five years following the procedure. Secondary aims are to assess growth and function of the transplanted valve. The hypothesis is that when compared to historical controls who have undergone conventional valve replacement, those undergoing partial heart transplantation will have valve growth that corresponds with somatic growth and superior valve function 1 year following the procedure. Up to five patients will be enrolled in this trial over three years.
The purpose of this post market surveillance is to continue monitoring the safety and effectiveness of the Berlin Heart EXCOR® Pediatric. This surveillance includes an "all-comers" prospective cohort of pediatric (\<22 years of age) patients implanted according to the IFU with the EXCOR® Pediatric.
Cardiac telerehabilitation is a much-needed pediatric therapy; however, a lack of randomized controlled trials has limited the development of and reimbursement for this valuable service. Through this prospective, randomized controlled trial, the investigators aim to demonstrate the safety and efficacy of PCTR in a clinically diverse population of children and adolescents with heart disease.
CMV infection and disease remain a significant clinical challenge for pediatric solid organ transplant (SOT) recipients. Current prevention strategies are limited to prophylaxis in which antiviral medication is administered for a period of several months or preemption in which close monitoring of CMV viral load from the peripheral blood is performed and treatment is initiated when CMV is detected. Each of these strategies has risks, costs, and limitations associated with it. Recently, assays for measurement of an individual patient's CMV immunity have been developed and are clinically available. One of these is the Viracor CMV T cell Immunity Panel. This flow cytometry based assay is performed on peripheral blood and measures cytokine release in response to CMV antigen stimulation by flow cytometry. The thresholds for this assay that confer protection against CMV infection in pediatric SOT recipients are not known. Defining CMV-specific cell mediated immune response thresholds that confer protection against CMV reactivation could inform patient specific durations of antiviral prophylaxis or pre-emptive surveillance testing. Therefore, the objective of this study is to quantify CMVresponsive T lymphocyte populations by flow cytometry (Viracor CMV T cell Immunity Panel) in pediatric heart, kidney, and liver transplant recipients within the first year of transplantation and to investigate potential threshold values that correlate with protection against CMV infection (DNAemia).
The goal of this study is to compare parent and child perceptions of wellness and vulnerability in children who have undergone solid organ transplant. It is hypothesized that there will be significant differences between parent and child perceptions.
Clinical evidence reveals that some patients who undergo cardiac transplantation exhibit problems with pulmonary vascular resistance as well. In some studies, an increase in pulmonary vascular resistance has been used as an indicator for increased 3-day and 3-month mortality after heart transplantation2. In this study, the investigators would like to look at pulmonary vascular resistance in patients with a surgical history of the Fontan procedure followed by heart transplantation.
Adherence to medical regimens refers to what degree a patient chooses to follow the advice given by his/her healthcare provider. Good adherence typically involves behaviors such as the patient taking medication as directed and going to scheduled clinic appointments. As many patients often do not follow the advice of doctors as closely as suggested, many researchers have tried to find out the reasons behind patients being "non-adherent." This research has looked at medical conditions such as diabetes, cystic fibrosis, and asthma. More recently, researchers have started to look at adherence with children who have undergone solid organ transplantation. This is because about 50% of these children are to some degree non-adherent with their medical regimen. This comes at a costly price as ongoing non-adherence in pediatric transplant can lead to the child's body rejecting the new organ and even death. This study has been designed to look at the reasons that pediatric patients may choose to be non-adherent. This study will look at issues related to the patient (e.g., age, family support), related to the disease and regimen (e.g., length of illness, how complicated the regimen is), related to the medication (e.g., taste, side effects), related to their mind (e.g., memory problems, confusion), and related to their emotions (e.g., being depressed, anxious). The investigators will be looking at each regimen-related behavior, such as attending clinic appointments and will be asking each family about any barriers that make it difficult. The investigators hope that knowing these barriers will help them make interventions that fit the specific issues that each patient faces. Ultimately, doctors, transplant coordinators, and psychological professionals will be able to use this information to intervene early with families who report barriers that impact adherence.
The purpose of this study is to examine the pharmacokinetics, pharmacodynamics, and pharmacogenomics of dexmedetomidine in the following three pediatric patient populations: patients with bi-directional cavopulmonary anastomosis or a Fontan procedure, patients who have had a cardiac transplant, and patients with otherwise normal physiology who are undergoing closure of a patent ductus arteriosis or atrial septal defect.
One of the risks associated with heart transplantation is failure of the graft. A graft is where the new heart is attached to the original vessels in the body. Approximately 10% of children suffer graft failure which, leads to heart failure and possible death. The problem is that we do not know some of the causes of graft failure thus, it is difficult to diagnose early and treat. Due to graft failure, lots of children are placed back on the transplant list and receive another new heart. In this study, we plan to perform a retrospective chart review looking to see if we can correlate graft failure with a problem with the vessels called coronary allograft vasculopathy or rejection. In order to do this, we will collect data from patient's charts that have been diagnosed with graft failure and compare their clinical presentation/data to pathology reports of the explanted hearts from these children. Explanted hearts are the old transplanted hearts that are removed in order to put a new heart into the body. Explanted hearts at our institution are always sent to pathology for analysis thus it will be quite easy to perform this review.