Clinical Research Directory

A Study of TCD601 in de Novo Renal Transplant Recipients

The purpose of this study is to evaluate the safety and efficacy of TCD601 in combination with Belatacept when compared to standard of care immunosuppression therapy in de novo renal transplant patients.

The Effect of Emotion-Focused Intervention on Emotion Regulation and Well-Being of Individuals With Transplantation

The study was designed to evaluate the effects of an emotion-focused intervention based on the Human-to-Human Relationship Model on emotion regulation skills and well-being in individuals who have undergone renal transplantation. This study was designed as a single-blind randomized controlled trial with a pretest, posttest, and follow-up control group design. Based on the data obtained from the study, the impact of an emotion-focused intervention based on the Human-to-Human Relationship Model on emotion regulation skills and well-being in individuals who have undergone renal transplantation will be evaluated.

Remimazolam Infusion in Kidney Transplant Patients: A Multicenter Study

The goal of this clinical trial is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of remimazolam (CNS 70754) in healthy adult participants. The main questions it aims to answer are: What are the key pharmacokinetic parameters of remimazolam, including peak concentration (Cmax), time to peak concentration (Tmax), area under the curve (AUC), and elimination half-life (T1/2)? What is the effect of remimazolam on consciousness, as measured by the MOAA/S scale and Narcotrend monitoring during anesthesia? Researchers will compare the pharmacokinetic and pharmacodynamic effects of remimazolam to see if the drug provides consistent and predictable sedation without significant adverse effects. Participants will: Receive continuous Infusion of Remimazolam. Have blood samples taken at various time points to measure plasma concentrations and calculate PK parameters. Be monitored for consciousness and sedation levels using the MOAA/S scale and Narcotrend. Undergo safety assessments, including laboratory tests, vital signs monitoring, and physical examinations throughout the study. This study will help determine the drug's behavior in the body and its impact on sedation, providing valuable information for its future clinical use in anesthesia and other medical applications. Last updated on December 22, 2024

Detection of Plasma DNA of Renal Origin in Kidney Transplant Patients

Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a potential diagnostic tool to monitor the rejection status of the kidney transplant. It has been suggested that dd-cfDNA is increasing in the blood of kidney transplant patient presenting a graft rejection. In this project, investigators proposed a different approach to predict and characterize kidney transplant rejection/dysfunction based on the quantification of epigenetic signatures present on the donor-cell-free DNA. In 2018, Moss et al. develops a deconvolution model capable of identifying the tissue origin of circulating DNA by taking advantage of its epigenetic properties. The study confirmed that the cell-free DNA circulating in healthy subjects comes mainly from blood cells and endothelial cells, but not from kidney cells. In this study, researchers investigate the evolution of blood renal-specific cell-free DNA amount in patient with chronic kidney disease before and after the transplantation surgery by testing a set of renal-specific epigenetic markers. The purpose of this study is to identify the biological noise of "native kidney" on renal-specific cell-free DNA and to compare it with signal coming from "transplanted kidney".

Evaluation of the Efficacy of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients"

The investigator hypothesizes that the combined use of (1) Donor-derived cell-free DNA (dd-cfDNA) in peripheral blood predicting anti-donor immunological activation or quiescence (2) interactive and actionable data analytics delivered at the bedside will promote safe clinical follow-up of kidney transplant patients with less need for invasive biopsy and less induced risk surveillance by allograft protocol biopsies to assess allograft rejection in clinically stable kidney transplant patients. In addition, the evaluation of the transcriptional changes in tissue samples in selected patients using automated processing of digital slide images and intragraft gene expression profiles will provide a better diagnosis of the rejection mechanisms to provide the best therapeutic approach as compared to current clinical practice. We therefore propose a French, multicenter, prospective randomized trial comparing two strategies of follow-up: in the first group, a biopsy is performed at M3, M12 and for clinical indication whenever considered necessary by the clinician during the first 18 months of follow-up after transplant. In the second group, patients will have the same follow-up as in the first group, but reports providing dd-cfDNA results and relevant medical parameters will be provided to the physician to help him in the decision to perform a biopsy or not.

Mesenchymal Stromal Cells in Living Donor Kidney Transplantation

Kidney transplantation is a good treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients receive induction therapy and immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. This research study will evaluate the safety and activity of mesenchymal stromal stem cells (MSCs) infusion compared to saline-only infusion in reducing the immune suppression necessary to achieve optimal renal function in renal transplant recipients. All participants will receive routine care: basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids.

Impact of the Use of Remote Monitoring in the Follow-up of the Renal Transplant Patient.

Transplant Centers are facing new organisational challenges with regards to the growing number of patients they have to follow-up. We have developed and assessed the feasibility of using a novel web application permitting a medically-tailored follow-up of stable renal transplanted outpatients: Ap'TELECARE. This novel approach is likely to facilitate the organization of patients' follow-up at the Transplant Centre level as well as to provide secondary individual benefits in terms of therapeutic education, adherence to treatment and eventually to improve long term outcome.

Optimal Dose of Anti-lymphocyte Globulin in Kidney Transplant Recipients With Low Immunological Risk

Antithymocyte globulins (ATG) are the gold standard of induction therapies and are currently used to prevent or treat acute rejection in solid organ transplantation. They induce rapid depletion of immune cells, particularly T lymphocytes. The time to immune reconstitution after ATG is characterized by significant intra- and inter-individual variability in reconstitution of immune cell subpopulations (T and B cells, NK cells, dendritic cells). This variability explains the prolonged T cell lymphopenia observed in some patients, which is a surrogate immune biomarker associated with an increased risk of death after 2 years of renal transplantation and more infections, cancers and atheromatous events. However, ATG also promotes an increase in the proportion of Treg cells. Although the underlying mechanisms are still debated, data from experimental animal models confirm the tolerogenic properties of ATG. ATGs are associated with improved allograft survival without rejection in patients at high immunological risk and are therefore indicated as first-line therapy in this population. In patients at low immunological risk, anti-CD25 monoclonal antibodies (anti-CD25mAb) are recommended as first-line therapy because ATGs are associated with a higher incidence of infections despite their equivalent efficacy in this population compared to anti-CD25mAb. However, neither the dosages nor the treatment duration of ATGs are clearly defined (recommended Grafalon® dosages range from 5 to 2 mg/kg/day for 5 to 21 days) and ATGs remain widely prescribed to allow early withdrawal of corticosteroids. Determination of optimal non-depleting doses of ATG could be of great interest because, in vitro, ATG is able to induce regulatory polarization of naïve T cells even at non-depleting doses. Thus, the use of such doses in patients with low immunological risk may be of interest in clinical practice with respect to anti-CD25mAb, particularly for their pro-regulatory properties and their low cost. This question must be clearly addressed in a pilot clinical study. The purpose of this study is to find the optimal non-depleting dose (Maximum Tolerated Dose; MTD) of rabbit anti-human T-lymphocyte immunoglobulin (Grafalon®) to prevent the complications associated with prolonged CD4 T cell lymphopenia in low immunological risk renal transplant recipients. The primary outcome for the de-escalation study is the Dose Limiting Toxicity (DLT) defined by a T cell (CD3+) relative depletion above 30 % compared to baseline (Day 0) at the end of the Grafalon® induction treatment (Day 4). The patients under study are adult receiving first kidney transplantation without a high immunological risk of rejection (african-American ethnicity, presence of a donor-specific antibody, blood group incompatibility, delayed onset of graft function (i.e donor after cardiac death), cold ischemia time \>24 hours, anti-HLA immunization (Flow PRA \> or = 20%, presence of donor specific antibody before and/or at time of transplantation and with a positive CDC and FXM with historical and/or transplant day sera), bacterial, viral or mycotic and parasitic infections, history of opportunistic infection that required intensive care hospitalization in the two years preceding the transplant, related donor with two-haplotype HLA matched kidneys, multi-organ transplant, history of cancer, thrombocytopenia \< 50 000 platelets/µl, hypersensitivity to the active substance or to the excipients of Grafalon (monosodium phosphate dihydrate, phosphoric acid). The inclusion period is one year. According to the active file of the center of Besançon, it is planned to include 2 patients per month. The maximum number of patients to include is 18. With a margin of error of 20%, it is possible to include all patients in 1 year. The duration of patient participation in the study is 1 year (one-year follow-up). Consequently, the duration of the study is estimated at 2 years (1 year of inclusion and 1 year of follow-up). ODORAT is a monocenter, open-label, de-escalation phase1b controlled study. The study will be proposed to patients receiving a first kidney transplant and matching the criteria of inclusion. Recruitment will be achieved only in Besançon's transplant unit. The physician gives information on the study and collect informed consent. Then the treatment is assigned according to the dose determined by the dose de-escalation study. The first dose tested is the dose level at 2 mg/kg/day (level 3). This dose is the reference dose according to the current recommendations. The number of patients included at each dose is determined according to Bayesian optimal interval (BOIN) design. The administration of treatment begin at time of transplantation according to recommendation. The study will include 11 visits: D0 (baseline) to D4 (primary end point assessement), D7, D14, M1, M3, M6 and M12, to analyze pharmacokinetics of Grafalon and the immune phenotype.

Knowledge of Cardiovascular Risk Factors in Chronic Kidney Disease Patients

The aim of this study is to assess knowledge of cardiovascular risk factors, physical activity levels, health literacy and perceptions of benefits and barriers to exercise in patients with chronic kidney disease and compare them with healthy people.

Muscle Oxygenation, Functional Capacity and Frailty in Kidney Transplant Recipients with and Without Inspiratory Muscle Weakness

The aim of this study was to compare respiratory function, muscle oxygenation, functional capacity, peripheral muscle strength, body composition, and frailty in kidney transplant recipients with and without inspiratory muscle weakness.

Exercise Capacity in Kidney Transplant Recipients

This study aimed to determine the determinants of 6 minute walk test distance in patients with kidney transplant recipients.

Flumazenil Antagonism of Remimazolam in Kidney Transplant Patients

To investigate the effect of different doses of flumazenil antagonism on remimazolam plasma concentration in patients undergoing renal transplantation under general anesthesia.

Effect of Probiotics on Immunosuppressive-drug-associated Diarrhea Among Renal Transplant Recipients

The goal of this pilot project is to 1) examine whether oral administration of probiotics are helpful in reducing immunosuppressive drugs-associated diarrhea and adhering to the required dose of immunosuppressive drugs and 2) determine how this treatment works by examining fecal microbiome and immunological markers among living and deceased donor renal transplant recipients. The main questions it aims to answer are: 1. Does low dose probiotics effective in reducing immunosuppressive drugs-associated diarrhea? 2. Does probiotics effective in reducing inflammation? 3. Is there any connection between fecal microbiome and immunological markers? Participants will receive one probiotics capsule or placebo capsule daily for 6 months from the onset of diarrhea post-surgically. Researchers will compare the data obtained through probiotics group and placebo group to answer the above mentioned research questions.

Dexmedetomidine and Kidney Transplantation

Dexmedetomidine, an alpha 2 agonist, is being increasingly used in recent years for the maintaining of anesthesia as it allows sedation and analgesia with only a modest respiratory depression effect when compared to opioids and inhaled anesthetic agents and allows maintenance of spontaneous ventilation. Most common side effects are bradycardia and hypotension. Drug's metabolism is exclusively hepatic and therefor do not require dosage adaptation for patient's kidney function. Post-Operative acute kidney injury (AKI) is a common complication after major surgery and might incur serious adverse outcomes such as longer hospital stay, dialysis, chronic kidney disease and death. The most common theory for the occurrence of post-operative AKI is the ischemic-reperfusion syndrome. Several in vitro animal studies as well as human studies have suggested the nephroprotective effects of per-operative continuous infusion of dexmedetomidine and its ability to decrease post-operative AKI. Kidney transplantation (KT) is the treatment of choice for patients with End Stage Renal Disease. It is considered a major surgery and it was shown that optimized perioperative management could improve post-operative outcomes such as early graft function as measured by urine output and serum creatinine trends. However, delayed graft function (DGF), which is defined by the need for dialysis within the first seven days after transplantation remains a significant issue for post-operative KT care with an incidence of up to 30%. A retrospective study of 780 patients receiving KT, has shown that preoperative dexmedetomidine could significantly decrease occurrence of DGF. Recently, two single-center, randomized controlled trials, with similar sample sizes of 104 and 111 patients, compared peri-operative continuous infusion of dexmedetomidine to placebo. One study failed to show significant impact on DGF incidence while the second showed a significant 50% reduction in DGF in the dexmedetomidine group. Due to increasing evidence concerning the nephroprotective effects and improved post-operative outcomes of perioperative continuous dexmedetomidine infusion, a larger, multi-center randomized-controlled trial to study and potentially confirm the evidence in the settings of KT would be of benefit. The aim of our study is to assess whether the perioperative continuous infusion of dexmedetomidine during KT could improve peri-operative renal function among KT recipients as compared to placebo.

Envarsus XR® in Adolescent Renal Transplant Recipients

Adolescents commonly experience barriers to adherence that entail forgetfulness, distraction, poor planning, and scheduling problems. A once daily oral regimen may be superior to the current regimens that require twice daily dosing. It is currently unclear if Envarsus XR® would improve outcomes in adolescent organ transplant recipients. Each patient will receive tacrolimus (twice daily immediate release oral formulation) which they are using as part of their standard of care immunosuppressive regimen for a portion of the study and Envarsus XR® (a once daily extended-release oral tacrolimus formulation) for a portion of the study in a cross-over design. Besides the advantage to adherence behaviors, a sustained-release tacrolimus preparation may decrease burdensome side effects and increase quality of life. Following enrollment, each patient will be maintained in the study for 9 months.

Combined Kidney and Hematopoietic Stem Cell Transplantation for Tolerance Induction

Combined transplantation of kidney and bone marrow between HLA-matched sibling donor-recipient pairs to induce immune tolerance in order to enable complete discontinuation of immunosuppressive therapy without kidney rejection. Hematopoietic stem cells are collected from the donor 4 to 8 weeks before kidney transplantation, CD34 cells are enriched by positive selection and cryopreserved. The day after kidney transplantation the recipient starts conditioning therapy with thymoglobuline, total lymphoid irradiation, steroids, tacrolimus and mycophenolate mofetil. Eleven days after kidney transplantation the stem cell graft is thawed and infused to the recipient. If mixed donor chimerism is successfully maintained more than 6 months without rejection, then immunosuppression may be tapered off until complete discontinuation.