31 Clinical Trials for Various Conditions
This is a randomized, double-blind, placebo-controlled trial in de novo kidney transplant patients to determine if the addition of belumosudil (brand name- REZUROCK®) on the background of standard immunosuppression will prevent fibrosis in the kidney transplant. Interstitial expansion is the precursor of interstitial fibrosis and graft loss. The hypothesis underlying the study is that abgrogating the fibrogenic effects of the RhoA pathway with belumosudil will reduce structural damage in transplanted kidneys and possible subsequent transplant failure.
Our group recently reported that tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, may be effective when administered monthly to patients with chronic antibody-mediated rejection (ABMR). The current paradigm to assess response to therapy involves serial monitoring for donor-specific antibodies, measurement of kidney function with creatinine, and periodic kidney transplant biopsies to survey for histologic findings indicative of ongoing ABMR. A new non-invasive blood test, donor-derived cell-free DNA (Allosure) has recently reported to have a high degree of discrimination for rejection and may be used to assess the likelihood of rejection. It has not been tested to see if it can be used to assess treatment response for rejection. This study will assess longitudinal changes in donor-derived cell-free DNA measurements in response to monthly therapy with tocilizumab for chronic ABMR and correlate these measurements to histologic changes on a follow-up kidney transplant biopsy.
In pediatric kidney transplant patients, rejection, medication toxicity and ischemia cause early and chronic renal allograft injury, which reduces graft lifespan and patient survival. Early detection of injury would facilitate prevention and treatment. The gold standard surveillance biopsy has limitations including delayed discovery of injury. No noninvasive test identifies graft injury before it is clinically apparent. This project's goal is to develop a novel early marker of subclinical graft injury to facilitate prompt recognition and treatment.
Doctors have had success preventing certain types of kidney transplant rejection by suppressing the immune system. However, an individual's genetic make-up and the strength of an immune response to a transplant may also determine whether a transplanted organ is rejected. The purpose of this study is to look at the genetic profile and immune response of people who have had kidney transplants and to correlate the findings with kidney transplant rejection episodes. Donor genetic profiles will also be studied and correlated with the recipient's information.
This is an open label safety and feasibility trial using Acthar® in addition to the investigators center-specific standard therapy, which could include increase in maintenance immunosuppression, high dose IVIG (intravenous immunoglobulin) (2 g/Kg), and/or Rituximab, in patients with chronic antibody-mediated rejection (CAMR).
A study to compare the conversion to Prograf® (tacrolimus) to the continuation of cyclosporine in patients at risk for chronic renal allograft failure
This study seeks to determine if administration of the drug belumosudil (KD025) will be safe and improve transplant tolerance in subjects undergoing combined Human Leukocyte Antigen (HLA) single haplotype-matched related or 0-3 antigen (at A, B, C, DR) HLA mismatched unrelated living donor kidney and hematopoietic stem cell transplantation.
The study seeks to determine if patients with a pre-existing, well-functioning kidney transplant from a HLA-identical living donor can be withdrawn from immunosuppressive medications without compromising allograft function through hematopoietic stem cell (HPSC) infusion from the same donor. HPSC infusion will be preceded by a conditioning regimen of total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG).
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).
This study is being done to test blood, urine and tissue samples to see if this can help decide if CKD (Chronic Kidney Disease), AR (Acute Rejection) and HCV (Hepatitis C Virus) can be identified in its early stages. CKD damage to the kidneys, AR and HCV all lower the body's ability to function properly. Early detection of these conditions could assist with successful treatment and possibly lead to less repeat organ transplants.
Hyperparathyroidism (HPT) is common in people with a kidney transplant. Patients with HPT often have high parathyroid hormone (PTH) levels and may have large parathyroid glands in the neck. Patients with HPT can develop bone disease (osteodystrophy). This bone disease can cause bone pain, fractures, and poor formation of red blood cells. Other problems from HPT may include increases in blood levels of calcium (hypercalcemia) and low blood levels of phosphorus (hypophosphatemia). The high calcium levels may cause calcium to deposit in body tissues. Calcium deposits can cause arthritis (joint pain and swelling), muscle inflammation, itching, gangrene (death of soft tissue), heart and lung problems or kidney transplant dysfunction (worsening of kidney transplant function). The purpose of this study is to evaluate the effects of cinacalcet (Sensipar/Mimpara) on high calcium levels in the blood in patients with HPT after a kidney transplant.
This study investigates the burden of disease among kidney transplant recipients that have developed Chronic Active Antibody Mediated Rejection (caAMR) compared with kidney transplant recipients that have not developed caAMR
The purpose of this study is to help researchers find out more about a condition called "Chronic Allograft Nephropathy" (CAN). CAN is a complication that sometimes occurs after kidney transplantation and affects the function of the transplanted kidney. It is hoped that by studying blood, urine, and tissue samples of kidney transplant patients, new ways of diagnosing and treating CAN may be found.
This trial investigates the efficacy and safety of clazakizumab \[an anti-interleukin (IL)-6 monoclonal antibody (mAb)\] for the treatment of CABMR in recipients of a kidney transplant.
In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.
The purpose of this study is to determine if analysis of urine samples for specific markers can predict transplant rejection in people who have received kidney transplants.
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.
Patients who have had a previous allograft failure represent a major problem for transplant centers as they are highly-human leukocyte antigen (HLA) sensitized and unlikely to receive another transplant without significant desensitization. This single center, phase I/II, open label single-arm exploratory study focuses on enrolling twenty patients (ages 15-75) who will begin desensitization therapy to achieve HLA incompatible (HLAi) renal transplantation. Patients who qualify will receive up to 6 doses of clazakizumab 25 mg monthly pre-transplantation. If patients receive an HLAi transplant during the study, the participants will continue to receive another 6 monthly doses of clazakizumab 25 mg, followed by a 6 month protocol biopsy. Patients will continue another 6 doses over 6 months if improvements are seen after the 6th dose of clazakizumab. Patients who develop evidence of persistent allograft dysfunction may have non-protocol biopsies for cause. Patients who receive 12 doses of clazakizumab post-transplant will receive a 12M protocol biopsy.
The purpose of this study is to determine whether the anti-T cell antibody, Thymoglobulin is a more effective induction medication than the anti-IL-2R inhibitor daclizumab, in kidney transplant recipients who have a positive crossmatch with their live donor.
Long-term graft failure rates continue to be unacceptably high despite the development of immunosuppressive drugs, underscoring the unmet need for robust prognostic biomarkers of allograft injury and failure. While rates of acute rejection (AR) continue to decrease, it remains the strongest predictor of long-term allograft survival, and so having a better understanding of factors predicting AR may contribute to more individualized patient care. Selecting optimum immunosuppressive dosage is another factor in personalizing kidney care. This project will study two areas of individualized kidney care: 1) assessing rejection by surveillance testing utilizing AlloSure, 2) developing an algorithm to select optimum immunosuppressive medication dosage.
This is a randomized, double-blind, placebo-controlled trial in de novo kidney transplant patients to determine if the addition of fingolimod (brand name Gilenya®, candidate name- FTY720) on the background of standard immunosuppression will prevent expansion of the interstitial compartment of the transplanted kidney. Interstitial expansion is the precursor of interstitial fibrosis and graft loss. The study will test the hypothesis that abgrogating the fibrogenic effects of both the RhoA and mTOR pathways with fingolimod will reduce structural damage in transplanted kidneys and possible subsequent transplant failure.
Antibody mediated rejection (ABMR) is a unique, significant and often severe form of allograft rejection. This single center, phase I/II, open label single-arm exploratory study focuses on enrolling ten patients with biopsy proven chronic antibody medicated rejection and/or donor specific antibody present at time of biopsy. Patients who qualify will be receiving clazakizumab (anti-IL6 monoclonal antibody) monthly x six doses. A protocol biopsy will be performed at 6 months and if improvement is seen, patients will continue another six doses for up to 12 months. For those completing 12 doses, there will be a 12 month protocol biopsy. For those who only received six doses, the next and last study visit will be at 12 months from enrollment. Total study duration is 12 months.
This is a prospective cohort observational study to assess the role of AlloSure Donor Derived Cell Free DNA (ddcfDNA) assay in the monitoring of three high-risk groups of kidney transplant patients for antibody mediated processes. * Group A. Thirty participants with a positive Virtual Cross-Match (VXM) at the time of transplant will be monitored for 12 months * Group B. Similarly, 24 participants with dnDSA will undergo a SOC biopsy within approximately three months to determine the incidence of Active Antibody Mediated Rejection (AMR) * Group C. 15 additional participants with the diagnosis of Chronic Active Antibody Mediated Rejection (cAMR) will undergo standard of care therapy and be monitored for treatment response with a follow-up biopsy at three months
The purpose of this study is to assess the safety, tolerability, and efficacy of efgartigimod PH20 SC given by a prefilled syringe in participants with Antibody-Mediated Rejection (AMR) after kidney transplantation. After a screening period of up to 6 weeks, eligible participants will be randomized in a 1:1:1 ratio. The study drug will be administered subcutaneously while patients remain on their standard background immunosuppression therapy (tacrolimus, mycophenolate mofetil, steroids) during the treatment period (48 weeks). At the end of the treatment period, the participants will enter an observational/follow-up period (approximately 24 weeks). The participants will be in the study for up to 78 weeks.
Chronic Allograft Nephropathy (CAN)/Interstitial fibrosis and Tubular Atrophy (IFTA) is responsible for most kidney transplant failures. CAN/IFTA on a 3 month kidney biopsy strongly predicts graft survival long term. CAN/IFTA remains a vexing problem for clinicians because current monitoring tools, namely the serum creatinine concentration, are not sensitive to early changes in glomerular filtration rate (GFR) or to histologic damage. Despite advances in prevention of acute rejection (AR), it is still a significant and potentially devastating complication of solid organ transplantation. One strategy to reduce the risk of rejection is to perform kidney biopsies to detect subclinical acute rejection (SCAR) and treat to prevent progression to rejection. There is evidence that treating SCAR can prevent further immune mediated injury to the kidney, a precursor to CAN/IFTA. Kidney biopsies provide better information but are limited due to safety concerns, patient preference and cost issues. Better, early and less invasive markers of CAN/IFTA will allow early intervention as well as improved graft and better patient outcomes. This study seeks to validate specific proteogenomic biomarker panels for AR and CAN/IFTA in a prospective blood, urine and kidney tissue monitoring study of kidney transplant recipients who will be scheduled for standard of care biopsies.
There is a need to develop blood and/or urine tests that will help to detect early signs of rejection in people who have had kidney transplant. Researchers will examine blood, urine, and tissue samples and try to identify genetic markers for certain conditions like rejection, response to therapy, and scarring of the kidney. By studying gene patterns, researchers hope to be able to diagnose these conditions earlier and improve kidney survival.
Alemtuzumab is a man-made antibody used to treat certain blood disorders. This study will evaluate treatment of kidney transplant recipients with alemtuzumab and other immune system suppressing medications with or without infusions of bone marrow stem cells from the kidney donor. The purpose of this study is to find out which strategy is more effective in preventing organ rejection and maintaining patient health.
This study will examine whether measurements of connective tissue growth factor (CTGF) and other cell proteins can identify which kidney transplant recipients are likely to develop chronic allograft nephropathy (CAN), a disease of the transplanted kidney. CAN may occur months to years after the transplant. The kidney becomes progressively scarred and eventually loses all function, so that dialysis or another transplant is needed. A better understanding of how CTGF and other proteins are involved in the development of CAN may provide new targets for treating for the disease. Patients who are scheduled to receive a kidney or combined kidney-pancreas transplant or who have received a transplant recently (within 6 months) may be eligible for this study. Participants will be enrolled before the transplant, if possible, or after the transplant, and will undergo the following tests and procedures: * Physical examinations at the screening visit, at 1, 6, 12, and 24 months, and then once yearly. * Blood sample collections at the screening visit, at 1, 6, 12, 18, and 24 months and then once yearly. * Urine sample collections at the screening visit, at 1, 6, 12, 18, and 24 months and then once yearly. * Kidney biopsies at the beginning of the study, at 1, 6, 12, and 24 months, and then once a year for research purposes. Participants may refuse to have a research biopsy at any time during the study. Also, patients who are having a kidney biopsy for another reason at these time points will not have a second biopsy. The biopsy procedure takes about 15 minutes and is done in the hospital. The patient lies on his or her back and the skin over the transplanted kidney is cleaned with alcohol and iodine. The area is numbed with an injection of an anesthetic, and then a biopsy needle is placed through the kin. The biopsy may be repeated up to three times to get enough tissue to test for CAN. Patients lie flat for 4 hours after the procedure to reduce the risk of bleeding, and are observed for another 2 hours for possible complications.
This study is intended to help doctors learn about the relationships between specific genetic makeup (gene markers) and the development of chronic rejection. This study is being done to see if there is a relationship between genetic patterns and the development of Chronic Allograft Nephropathy (CAN). Medical scientists also hope to learn more about how genetic differences between people determine their response to a drug or a disease by storing a small blood sample in a special "bank". This sample may be tested at some point in the future in an attempt to better understand the factors that may influence rejection, transplantation outcomes and transplant success rates.
The purpose of this study is to see how effective 2 drugs, irbesartan and pravastatin, are at slowing kidney transplant failure. Many kidney transplant patients have some type of chronic rejection. Chronic rejection is a disease that causes scarring and damage to the kidney. Over time, chronic rejection can lead to kidney failure, making it necessary for patients to start dialysis and possibly receive another kidney transplant. Doctors would like to see whether irbesartan and pravastatin can slow this damage and prevent kidney failure in patients with signs of chronic rejection.