Clinical Research Directory

A Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Simultaneous Kidney Pancreas Transplant Recipients

BEAT-BK will see the effect of immunosuppression reduction/modification with and without IVIG on BKPyV infection, allograft function, allograft loss, acute transplant rejection, immunosuppression load and death in kidney and simultaneous kidney pancreas transplant recipients with polyomavirus infections (BKPyV).

(TNX-1500) in Kidney Transplant Recipients

The primary objective is to investigate the safety and efficacy of TNX-1500, an FC-modified anti-CD154 mAb, in five kidney transplant recipients at 12 months.

ECP-DL Cell Infusion for Induction in Living Donor Kidney (LDK) Transplants

This is a phase 1 trial, 36 month duration for subjects with end-stage renal disease (ESRD). The objectives of the trail are1) Determine the safety of ECP-DL cell infusion in living donor renal transplant recipients. 2) Determine rates of graft rejection and compare to historical controls. One week prior to planned LDK transplant the donor and recipient pair will be seen for ECP-DL preparation and infusion. Donors will undergo one single unstimulated peripheral blood mononuclear cell collection using the THERAKOS® CELLEX® Photopheresis System; the cell product will then undergo ECP treatment to make ECP-DL, which will then be infused into the recipient. One week later, recipients (n=12) will undergo LDK transplant using standard of care maintenance immunosuppression without antibody induction therapy. Subsequent patients will receive cell infusions in escalating cell doses. A minimum of two months will be used as an interval between ECP-DL treatment in each tier. A staggered approach for moving to the next tier will be employed waiting no less than two months to ensure absence of adverse events using the following tier dosing schema: Tier 1: 0.5 x 10\^9 ECP-DL treated cells (n=4) Tier 2: 1 x 10\^9 ECP-DL treated cells (n=4) Tier 3: 2 x 10\^9 ECP-DL treated cells (n=4) Following transplant, LDK recipients will undergo ECP using the Therakos system on two consecutive days per month for 6 months (12 treatments). Peripheral IV access will be used whenever possible.

Immunological Tolerance in Patients With Mismatched Kidney Transplants

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.

Delayed Immunological Tolerance in Patients With Well-functioning Pre-existing HLA-matched Kidney Transplants

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).

To Explore the Application Value of Magnetic Resonance Imaging in Noninvasive Quantitative Evaluation of Graft Function and Systemic Metabolism After Renal Transplantation

At present, renal biopsy is the gold standard for evaluating the pathology of renal transplants, but it is invasive and has the risk of serious complications; and the sampled tissue is only a small part of the kidney, which is prone to sampling bias and lacks reliable and comprehensive detection results. Therefore, it is an urgent problem to develop a non-invasive dynamic detection method for renal insufficiency and transplanted kidney. With the continuous development and updating of technology, imaging provides a new way for non-invasive evaluation of renal allograft pathology including rejection reaction, acute renal allograft injury, viral infection, etc. MRI technology has developed the diagnosis of renal allograft rejection, fibrosis and other renal allograft dysfunction from macroscopic simple biomorphological changes to microscopic complex pathophysiological changes due to its high resolution of soft tissue and its ability to perform multi-parameter analysis. In recent years, under the background of precision medicine, artificial intelligence technologies such as radiomics and machine learning are rapidly becoming very promising auxiliary tools in the evaluation of transplanted kidney images. They can extract and learn features in images with high throughput, make greater use of information that cannot be recognized by human eyes in medical images, and realize disease diagnosis, prognosis evaluation, and curative effect prediction by establishing models. However, most of the current research is in the preliminary stage. There are few evaluation studies on kidney transplantation. It is believed that with the continuous improvement of algorithms and optimization of models, radiomics and machine learning will make great progress, which will promote the development of individualized and precise medicine for patients with renal insufficiency to a certain extent.

Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant

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.

Fingolimod for the Abrogation of Interstitial Fibrosis and Tubular Atrophy Following Kidney Transplantation

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.

Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced NK-mediated Rejection

Background: Long-term success of organ transplantation is limited by the inexorable loss of graft function due to rejection. Prevalent dogma defends that allograft rejection is exclusively mediated by the adaptive immune system: T cells are responsible for cellular rejections and B cells producing Donor Specific Antibodies (DSA) are responsible for humoral rejection. Recently, we demonstrated that innate NK cells could be implicated in the generation of chronic vascular rejections lesions by sensing the absence of expression of self Major Histocompatibility Complex (MHC) class I molecules ("missing self") on graft endothelial cells with their Killer cell immunoglobulin-like (KIR) receptors. Using human in vitro and murine in vivo models, we also showed that Mammalian Target Of Rapamycin (mTOR) inhibitors could efficiently prevent this new kind of rejection. Objective: The aim of our project is therefore to test in a cohort of kidney transplanted patients the efficiency of mTOR inhibitors to treat this new kind of rejection Methods: A cohort of 20 kidney transplant patients with a missing self on their graft responsible for a NK-mediated rejection will be established prospectively. An mTOR inhibitor will be introduced in these patients for 6 months in association with a calcineurin inhibitor and corticosteroids. Graft function, histological lesions and NK activability will be monitored following this modification of treatment.

Home Based Monitoring of Kidney Transplants Utilizing Capillary Microsamples

Renal transplant recipients are followed as out patients at the transplant center for about 8 weeks after surgery. Between 1-2 weeks after surgery, 50 standard immunological patients will be randomized (1:1) to either follow standard of care (SOC) or having every second poli clinical visit without entering the hospital HBM; Home Based Monitoring). They are to take a capillary finger-prick blood sample themselves, send it to the laboratory for analysis and then they will get a telecom follow-up that day from their transplant physician. Outcome is no difference with regards to being able to follow the randomized follow-up procedure.

Assessment of QSant™ for Underlying Allograft Rejection

The AQUA registry is a multi-center observational study to assess the clinical management of kidney transplant recipients (KTRs) with use of the QSant test. QSant is a test based on 6 urinary biomarkers including cell-free DNA, that is used for the evaluation and management of acute rejection in renal allograft recipients with clinical suspicion of rejection, as well as subclinical rejection.

Tacrolimus Pharmacokinetic Subpopulations

This prospective study will investigate the concentrations of tacrolimus metabolites (M-I and M-III) over the four first years post-transplantation. A differential metabolism might result in different metabolites' concentration and explain a kidney survival difference between "high rate metabolism" (defined as a concentration/dose ratio, C/D ratio, lower than 1.04 µg/l/mg) and other patients. The primary endpoint is therefore to compare tacrolimus metabolites' concentrations with respect to the group, either \< or \>= 1.04 µg/l/mg, in order to detect differences in tacrolimus metabolization between these groups.