View clinical trials related to Ischemia Reperfusion Injury.
Filter by:A first-in-human single center, randomized, double-blind, placebo-controlled trial, with primary objective to evaluate safety and tolerability of ex-vivo kidney allograft treatment with TUM012 to reduce ischemia-reperfusion injury in de novo kidney transplant recipients.
The number of patients with end stage renal disease is increasing continuously and kidney transplantation is the preferred treatment modality. Modern immunosuppressive therapy has reduced the number of acute rejection episodes and increased one year allograft survival dramatically. Nonetheless, 4% of allografts are lost beyond the first year annually due to a multifactorial process and the latter number has not changed for decades. One of the most important factors to determine long-term success after kidney transplantation is the quality of the donor organ. For example, transplantation of organs from elderly or extended criteria donors results in reduced allograft and patient survival. In previous work, the investigators specifically focused on age-associated molecular signatures including telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) and assessed these parameters in pre-implantation biopsies of 54 patients. In a linear regression analysis CDKN2A turned out to be the best single predictor for serum creatinine after 1 year followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values. In another study the investigators were able to show an interaction between donor age and use of calcineurin inhibitors with regard to outcome after renal transplantation. During these past activities an extensive set of whole genome transcriptomics profile information from zero hour biopsies and clinical follow-up data has been collected. In the TOPVAS study, existing data derived from 72 of the above mentioned set of biopsies (exclusion of live donor grafts) will be analysed with state of the art bioinformatical/system biology tools to derive a general (not purely age associated) prognostic biomarker panel for functional transplant outcome two years after transplantation. This marker panel will also be used to define organs preferentially suitable for MMF/tacrolimus based immunosuppression. Both panels will then be validated for their prognostic and predictive information on the long-term outcome after transplantation in a new independent patient population treated with tacrolimus and MMF. In addition to biomarker assessment and in pursue of identifying alternative and/or complementary parameters with predictive value , an advanced morphological investigation of tissue biopsy life stains will be performed employing an innovative cell viability staining technology ("BIOPSYCHRONOLOGY").
Ischemia perfusion injury (IRI) is a major cause of organ injury during kidney transplantation. Currently there are no treatments for IRI other than dialysis. Preliminary studies in female mice have found protection from IRI when given short term estrogen supplements. This study will look at the effect of intravenous estrogen given peri-operatively to reduce the effect of IRI in female kidney transplant recipients.
Ischemia reperfusion injury may be attenuated by HO-1 induction. Heme arginate showed protective effects during prolonged ischemia in animal studies. Functional blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) shall evaluate the effects of HO-1 induction during short-time ischemia in skeletal muscle of healthy subjects.
The study is designed to assess the feasibility of evaluating YSPSL for the amelioration of ischemia reperfusion injury following liver transplantation by administering YSPSL into the liver graft directly ex vivo via the portal vein and to the recipient intravenously prior to reperfusion. This study is an extension of the recent pilot study YSPSL-0002 with an almost identical study protocol. The rationale of this and the previous study is based on the recent observation that P-selectin expression has been associated in liver grafts with prolonged cold storage times and rejection. By examining biomarkers of IRI including P-selectin by immunohistochemistry and/or quantitative PCR, liver histology and hepatic blood flow using established techniques, the goal of this study is to evaluate the feasibility of using these modalities for future studies of safety and efficacy.