View clinical trials related to Immunosuppression.
Filter by:World Health Organization considers non-adherence has a strong negative impact on the health of patients with chronic diseases. In transplantation, adherence to immunosuppressive drug regimens associates with late rejection and graft loss making it a critical determinant of patient outcome. The prevalence of non-adherence in transplant patients, including liver transplant patients, can be as high as 40%. Among others, life-long intake and complexity of immunosuppressive regimen make patients prone to non-adherence. For instance, non-adherence is more prevalent among patients with higher numbers of immunosuppressive drugs. One of the most commonly cited causes of non-adherence is forgetfulness and disruptions in routine, with the evening dose of twice daily regimens being the most likely to be affected6. Besides non-adherence, the constraints generated in everyday life by immunosuppression (including timely and regular drug intake) and the complexity of the immunosuppressive regimens represent a burden for the patients and are probably associated with a health-related quality of life deterioration. Therefore, long-term adherence and quality of life after liver transplantation might be improved by using a well-tolerated and easy-to-handle immunosuppressive regimen. The immunosuppressive regimen after liver transplantation is in most cases based on different combinations of tacrolimus, mycophenolate mofetil and corticosteroids. While corticosteroids are administered once daily, tacrolimus can be administered either twice-daily (BID) as an immediate-release, or once-daily (QD) as an extended-release formulation. Among once-daily tacrolimus formulations, LCP-tacrolimus (ENVARSUS XR®) is approved for the prevention of transplant rejection in adult liver allograft recipients. It has demonstrated similar outcomes compared to immediate-release tacrolimus BID, in both kidney and liver transplantation. Mycophenolate has only been approved for BID administration, preventing from taking all immunosuppressive drugs once daily. Yet, single daily dosing would probably contribute to better adherence and quality of life in patients receiving a life-long treatment. Although the half-life of mycophenolic acid (MPA), the active moiety of mycophenolate mofetil (MMF) is compatible with once-daily administration, no published randomized clinical study has ever evaluated the efficacy and safety of MMF administered QD. The narrow therapeutic index and wide pharmacokinetic variability of tacrolimus and mycophenolate justify individual dose adjustment by means of therapeutic drug monitoring (TDM), in order to minimize the risk of acute rejection and the occurrence of adverse events. For tacrolimus, TDM is generally based on the trough concentration (C0) and sometimes on the area under the concentration-time curve (AUC), while for mycophenolate it should be based on the AUC of MPA. However, the dose adjustment of MMF in liver transplant patients is most of the time performed a posteriori, based on clinical signs of inefficacy of toxicity. Limited sampling strategies with maximum a posteriori Bayesian estimation have been developed by our team for both molecules in adult liver transplant patients to estimate their AUC, which is considered the best marker of exposure for both. Therefore, tacrolimus AUC0-24h can be estimated by Bayesian estimation using samples collected before administration (C0), 8 (C8h) and 12 (C12h) hours after the administration of ENVARSUS XR®, or 1 and 3 hours after the administration of PROGRAF® and ADVAGRAF®. For mycophenolate, the MPA AUC can be estimated using samples collected 20 min, 1 and 3 hours after MMF administration, by Bayesian estimation. Even if limited to 2 or 3 blood samples, tacrolimus TDM for ENVARSUS® requires late sampling (12h post-dose). To overcome the necessity of a longer hospital stay, microsampling devices (MSD) such as the Volumetric absorptive microsampling (VAMS®) device (Mitra®) can be used by the patients to take samples themselves, at home. Moreover, they are less invasive than venipuncture and collect low but accurate volumes of blood for analysis. In this context, we propose a randomized controlled non-inferiority study to demonstrate that in liver transplant recipients, an immunosuppressive strategy based on single daily doses of LCP-tacrolimus (ENVARSUS XR®) and mycophenolate mofetil (CELLCEPT®) started at M6 post-transplantation is not inferior to XR-tacrolimus (ADVAGRAF®) and MMF administered BID, in terms of incidence of treatment failure (see below) at the end of the first year after transplantation, and to obtain adherence, quality of life and safety data. In order to compare solely MMF QD to MMF BID, patients on ENVARSUS XR® and MMF QD will be compared to a third group of patients receiving ENVARSUS XR® and MMF BID. A direct comparison of efficacy and safety, quality of life, adherence and exposure indices will be performed between ENVARSUS XR® and ADVAGRAF®.
Medical data and biological samples obtained from transplant patients are collected and managed across Germany with the help of the DZIF Transplant Cohort. The data and samples form the basis of scientific studies which investigate the connections between numerous factors influencing an organ's susceptibility to infection and organ function.
The goal of this study is to measure concentrations of the drug tacrolimus in both whole blood and within T lymphocytes. It will also learn on the correlation between the concentration in T lymphocytes and the effects of the drug. The main questions are: (i) What is the ratio between the tacrolimus concentration within T lymphocytes and in whole blood?; (ii) What is the correlation between tacrolimus concentrations and the effects of the drug? Participants will: - Receive standard clinical care; - Undergo two extra venipunctures for the collection of blood.
The investigators will evaluate the immune response of immunocompromised adults, who have previously received at least 1 dose of 23-valent pneumococcal polysaccharide vaccine, to the booster series of 15-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine 8 weeks later. Immune response will be assessed by opsonophagocytic assay reactivity and IgG Geometric mean concentration changes.
The goal of this clinical trial is to compare the bioavailability and practicability of two different formulations of tacrolimus in kidney transplant recipients. The main objective is to demonstrate that Envarsus® (test drug) has superior (higher) oral bioavailability compared with Advagraf™ (comparator drug) at 12 weeks after kidney transplantation. The trial also aims to compare the practicability (handling) of the two drugs using a series of pharmacokinetic parameters and to explore the relationship between drug bioavailability and long-term clinical outcomes, with a special focus on dose-dependent adverse reactions, measured until 3 years post-transplantation. The trial incorporates a pharmacokinetic sub-study designed to profile the peak tacrolimus blood concentration up to 6 hours after drug intake on the day of the 12-week study visit.
The goal of this clinical trial is to compare responses to Varicella Zoster vaccination between kidney transplant patients on different medication regimens, and their healthy co-habitants. The main questions it aims to answer are: 1. Are there differences in vaccination immunological responses in kidney transplant patients on different immunosuppression regimens? 2. Are there differences in vaccination immunological responses between kidney transplant patients and their healthy co-habitants? Participants will all receive a 2-dose course of SHINGRIX recombinant Zoster vaccination, and have immunological responses measured and compared at 5 timepoints between 1 week to 1 year post-vaccination.
The goal of this clinical trial is to learn about the efficacy and safety of immunosuppressive withdrawal in pediatric liver transplant recipients. The main question it aims to answer is:exploring the landscape of immune tolerance after pediatric liver transplantation. Moreover,this clinical trial aims to provide important foundation and clinical data for inducing immune tolerance, as well as to clarify the mechanism of immune tolerance development in pediatric liver transplantation, identify biomarkers that can be used to predict immune tolerance, and build a prediction model of immune tolerance after pediatric liver transplantation. The study planned to enroll 47 recipients after pediatric liver transplantation which would gradually withdrawal immunosuppressive after enrollment, divided the participants into immune tolerance and immune intolerance groups based on the outcome of immunosuppressive withdrawal.In this study, we collect the peripheral blood and liver biopsy samples from the two groups, find biomarkers with predictive value for immune tolerance in recipients after pediatric liver transplantation, and build a predictive model of immune tolerance by machine learning.
To determine whether providing a recombinant booster COVID-19 vaccine improves sustained humoral and cell-mediated immunogenicity against SARS-CoV-2 in immunosuppressed patients with Inflammatory Bowel Disease (IBD) and/or solid organ transplant recipients. 120 participants will be enrolled and can expect to be on study for 6 months.
Immunotherapy have revolutionized the field of oncology, but response rates are low and all patients relapse, due to cellular and soluble immunosuppressive mechanisms. MDSC are one of the most important immunosuppressive cells, that also harbour non immunologic functions, favouring cancer invasion. These non immunologic functions of MDSC in lung cancer will be better characterized. Indeed, cellular mechanisms will be analysed by in vitro studies, assessing the effect of immunosuppressive cells, provided by fresh tumor samples, on phenotype and functions of lung cancer cell lines. The aim of this study is to better characterize immunosuppressive landscape of NSCLC and mechanisms involved in their protumor functions.
Objective: To investigate whether replacement of MMF/MPA by everolimus in kidney transplant recipients results in superior immunogenicity of COVID-19 vaccination as measured by neutralizing antibody titer against the Omicron XBB.1.5 strain. Trial design: Multicentre, open-label randomized controlled clinical trial, for a duration of at least 10 weeks with an optional extension to 18 weeks. Trial population: Kidney transplant recipients, 18 years or older, who are at least 6 months after transplantation, with a functioning kidney transplant, using MMF/MPA in combination with at least one other immunosuppressant including a calcineurin inhibitor (CNI), with at least 3 previous COVID-19 vaccinations (=basic COVID-19 immunisation). Interventions: Patients will be randomized into one of two equally sized groups, with either continuation of their current immunosuppressive regimen including MMF/MPA or replacement of MMF/MPA by everolimus during at least six weeks before until four weeks after the last vaccination. Patients will receive a repeated COVID-19 vaccination with the monovalent Omicron XBB.1.5 vaccine, 28 days thereafter they can opt to also receive two herpes zoster vaccinations with the Recombinant Zoster Vaccine (RZV) with an interval between the first and second dose of 28 days. Main trial endpoints: The neutralizing antibody titer against the Omicron XBB.1.5. strain 28 days after monovalent Omicron XBB.1.5 COVID-19 vaccination in patients continuing MMF/MPA compared to patients who switched to everolimus. Secondary trial endpoints: - SARS-CoV-2 specific anti-S1 antibody level at 28 and 56 days after COVID-19 vaccination - Varicella zoster specific anti-gE antibody level 28 days after 1st and 2nd herpes zoster vaccination - SARS-CoV-2 specific T-cell response 28 days after COVID-19 vaccination - Varicella zoster specific T-cell response 28 days after 2nd herpes zoster vaccination - Safety in terms of incidence of acute rejection, kidney function decline, SAEs, AESIs and solicited local and systemic AEs after COVID-19 and herpes zoster vaccination