11 Clinical Trials for Various Conditions
The AlloSure test is approved by the Centers for Medicare \& Medicaid Services (CMS) for use in Medicare patients to assess the probability of allograft rejection in kidney transplant patients. The pivotal DART study discusses the use of the non-invasive AlloSure test to measure donor derived cell-free DNA (dd-cfDNA) and the Allosure test can by used to discriminate active rejection in renal transplant patients. Pancreas allograft rejection still remains a major clinical challenge and is a primary cause of death censored pancreas allograft loss. Pancreas transplant rejection is diagnosed by biopsy, however it is not commonly performed because of the complications such as pancreatic leak, graft loss and patient death. Currently at Rush surveillance biopsy of the pancreas are not performed routinely due to the above risks. At RUMC, patients are followed post-transplant with series of labs at set intervals that include lipase, DSA, C-Peptide, and GAD65 for surveillance of rejection The AlloSure test was introduced for routine use in kidney transplant recipients at Rush University Medical Center in October 2017, after CMS approval and then as part of the KOAR Study in May of 2018. AlloSure test has been included as part of the routine labs for surveillance of rejection in pancreas transplant recipients at RUMC since September 2018 after it was approved for compassionate use. The addition of AlloSure has helped to improve surveillance of rejection in pancreas transplant recipients and has reduced the need for the kidney biopsy as a surrogate marker of rejection in the pancreas. Our goal is to determine if AlloSure can be used for surveillance for rejection in recipients of Simultaneous Pancreas and Kidney (SPK) Transplant recipients.
Although the notions that kidney transplantation is the treatment of choice for patients with end-stage renal disease and that simultaneous kidney and pancreas transplant is the only treatment able to restore euglycemia in patients with type 1 diabetes and selected patients with type 2 diabetes, are now consolidated, rates of transplantation remain low among potential candidates with high levels of preformed anti-HLA antibodies. Most of the data comes from the experience in kidney transplant but can be easily translated to pancreas transplant. Approximately 30% of patients on the transplant waiting list have evidence of sensitization in the form of alloantibodies, generated from exposure to previous transplants, blood transfusions, pregnancy, or other events. The presence of a panel-reactive antibody level of at least 80% (i.e. a high level of sensitization) creates difficulty in finding matched kidneys from compatible donors, leading to lower rates of transplantation in highly sensitized candidates compared to non-sensitized; the longer waiting times translates in an increased mortality rate. Despite the development of desensitization strategies and the advancement in immunosuppression protocols, it is apparent that transplanting these patients carries an increased risk of acute antibody mediated rejection; 25%-50% of transplants will have an early acute antibody mediated rejection . Most of these rejections can be successfully treated, but a high rate of transplant glomerulopathy and chronic antibody mediated rejection (AMR) leading to accelerated allograft failure is common.
Hypothesis 1: 18F-Fluciclovine PET/CT can correctly and easily identify the pancreatic allograft and determine its viability Aim 1: Assess whether 18F-Fluciclovine can identify the pancreatic allograft accurately and assess its viability and visibility Hypothesis 2: 18F-Fluciclovine PET/CT uptake in the pancreas (SUV) is related to total pancreatic function and therefore can indicate whether the pancreatic allograft is at risk of rejection Aim 2: Assess whether 18F-Fluciclovine uptake in the pancreas can be a surrogate for pancreatic function
This is an observational study for patients with type 1 diabetes, whom are already scheduled to have desensitization treatment to help increase the chance of receiving a pancreas transplant.The study staff will be looking at medical records in order to collect past, present and future information for each subject's medical condition and/or transplant. There are no additional study tests, procedures or devices needed for our analysis.
The purpose of the study is to determine the safety and efficacy of two dosing regimens of daclizumab in simultaneous kidney/pancreas transplant recipients.
The purpose of this research study is to compare the effects of the two most commonly used anti-T cell induction agents(alemtuzumab and rabbit anti-thymocyte globulin) to prevent rejection in kidney and pancreas transplant patients. Alemtuzumab is Food and Drug Administration (FDA) approved for treating a certain type of cancer (leukemia), and Thymoglobulin® (rabbit anti-thymocyte globulin) is approved for anti-rejection treatment, but neither drug is FDA approved for administration at the time of transplantation to help prevent rejection. Even so, many transplant centers use these medications at the time of transplantation and believe that their use helps to decrease the risk of developing rejection following kidney and pancreas transplantation. Which drug might be better is not known. Subjects will receive either alemtuzumab (one administration) or rabbit anti-thymocyte (3 to 7 doses) at and within the first week of transplantation. Subjects will be assigned to either the alemtuzumab or rabbit anti-thymocyte globulin groups by chance. The two groups will be compared to see if there are meaningful differences for survival, organ function, side effects, and quality of life. The follow-up care after transplant for subjects in the study is the same as that for patients who are not in the study, except that a quality of life questionnaire (estimated to take 10 minutes to complete) will be completed at the time of transplant and through year 2 during selected scheduled clinic visits. A retrospective chart review will occur at 3-5 years post-transplant to follow incidence of chronic rejection, patient and graft survival and graft function.
This is a non-randomized, non-interventional, prospective pilot cohort study to monitor SPK patients post-transplant to determine if non-invasive measures using dd-cfDNA (Allosure) and AlloMap can assess an array of immune panels to predict and confirm the development of allograft injury and rejection in either organ. Aims of the study 1. To develop and validate AlloSure and AlloMap in SPK transplant recipients with stable allograft function and in diagnosis of acute TCMR and ABMR in either organ 2. To assess the ability of AlloSure and AlloMap to determine early discordant rejection in SPK recipients 3. To investigate AlloSure and AlloMap in SPK transplant recipients with diagnosis of BKV viremia
CMV viral disease negatively affects transplant patients. CMV is the most prevalent infection in transplant patients and 3 month drug regimens to prevent the virus have been mostly unsuccessful, usually after the drug has been stopped, the patient develops the viral disease. Extended use of anti-viral drugs may, in fact, may lead to the development of resistant virus. We hypothesize that extended use (12 months) of valganciclovir (Valcyte™)will not only be efficacious but will not be associated with the development of resistant CMV. Sample Size: 100 patients at 3 sites have been enrolled Patient Selection: Adult (\>18 years) recipients of cadaveric or living donor kidneys, pancreas, or combine kidney-pancreas transplants. Immunosuppression: To be determined according to each center's standard protocol (s). Study Drug: Valcyte™ Days 0 - 90: All Patients, 900 mg QD Days 91 - 365: Group 1: 900 mg QD Group 2: 450 mg QD Assessment of Valgancicovir (Valcyte™)Resistant CMV : Serial serum samples (at transplant, 6 weeks, and 3, 6, 9 and 12 months post-transplant) for PCR amplification and DNA sequence analysis from detectable CMV to identify the presence of mutations within the UL97 and UL54 genes. Other Analyses: Additional information will be evaluated relating to the development of CMV disease, development of ganciclovir toxicity, graft rejection or graft loss and patient death. Preliminary information regarding the predictive value of DNA assays for the development of CMV disease will be evaluated.
This protocol facilitates the development of methods for determining whether transplant recipients have developed immune hyporesponsiveness or tolerance towards their allograft. These methods will involve the study of peripheral blood or biopsy tissue obtained at regular intervals from patients receiving kidney or combined kidney-pancreas allografts at the Warren G. Magnuson Clinical Center. In addition, patients that have previously received a kidney or combined kidney-pancreas allograft will be evaluated using assays requiring peripheral blood mononuclear cells and/or biopsies. Assays developed under this protocol will be used in subsequent protocols to assess the effects of immune modulating treatment regimens and may eventually be used to direct clinical care or guide the withdrawal of immunosuppressive agents. However, patients enrolled in this protocol will not have any change in treatment based solely on the assays developed without being enrolled in an additional study.
Pancreatic islets are the part of the pancreas that produce insulin and help control the blood sugar. This study aims to improve islet transplantation as a treatment for Type 1 Diabetes by using a new combination of immunosuppressive drugs that have been successful in treating other autoimmune diseases and in preventing kidney transplant rejection.
Donor-derived cell-free DNA (dd-cfDNA) has shown promise as an early marker for cellular injury caused by rejection. dd-cfDNA changes may also indicate other injuries that lead to progressive decline in transplant organ function associated with, in the case of kidney transplantation, the presence of interstitial fibrosis (IF) and tubular atrophy (TA) seen in biopsy specimens. Here, we will study the utility of dd-cfDNA to predict rejection in pancreas and pancreas-kidney recipients.