Clinical Trials Logo

Clinical Trial Summary

Kidney transplant patients under an immunosuppressive treatment based on anti-calcineurin and mycophenolate-mofetil and induction therapy with rATG who suffer from early systemic viral replication by the CMV virus could benefit from the introduction of an i-mTor drug. (everolimus) to replace mycophenolate mofetil. This conversion would be effective in slowing down and controlling viral expansion without the need to initiate any prophylactic anti-viral therapy thanks to the activation of the CMV-specific cellular effector response or to an antiviral effect of i-Mtor itself.


Clinical Trial Description

Human cytomegalovirus (CMV) is the most common opportunistic pathogen in the first months after solid organ transplantation, being associated with an increased risk of acute and chronic graft rejection, graft loss and an increase in patient mortality. The susceptibility to developing CMV infection is essentially determined by the host's immune status against the virus, with seronegative recipients (IgG-) receiving a graft from a seropositive donor (IgG +) (R- / D +) being the group with an especially high risk of developing CMV infection and disease after transplantation. In fact, without the administration of a preventive therapy for CMV, around 60-70% of this risk group will present viral infection (replication of copies of CMV in blood) and up to 30% will develop systemic disease (viral invasion of the tissue). However, the incidence of infection among R + / D + seropositive (IgG +) patients under treatment with induction with anti-IL2RA and the combination of mycophenolate mofetil (MPA) and anti-calcineurin drugs (CNI), can reach up to 40%, and up to 60% if induction therapies are administered with T-lymphocyte depletors with polyclonal antibodies (Thymoglobulin®, rATG) (6). All this suggests that the assessment of the immunological risk of developing post-transplant CMV infection is relatively poor and that the humoral response to the virus does not fully explain the patient's immunological susceptibility to the virus. In this sense, it is well known that the subpopulation of CMV-specific memory / effector T cells plays a key role in the control of viral survival replication in general and of CMV in particular. While it has been reported that CD8 + cytotoxic T cells have the ability to activate against a wide range of immunogenic proteins of the CMV virus, it appears that high frequencies directed against the major CMV antigens such as those of immediate expression-1 (IE-1) and phosphoprotein 65 (pp65) play a critical role in the control of CMV viral replication. One of the most precise functional techniques to study the cellular memory immune response is the IFN-γ ELISPOT test, which allows knowing the antigen-specific response at the individual cellular level, thus providing high sensitivity and specificity. Along these lines, our group and others have shown how the monitoring of the CMV-specific cell response with the IFN-γ ELISPOT test, both before and after transplantation, is capable of identifying those patients with a high risk of developing infection by CMV, regardless of immunization status. In addition, data from a prospective, randomized clinical trial led by our group, evaluating the cellular response to CMV before transplantation using the IFN-γ ELISPOT test, have confirmed the high negative predictive power in identifying those patients with high risk of developing viral infection after transplantation, despite being serologically positive. Mtor (mammalian target of rapamycin) inhibitors, everolimus and sirolimus, are a class of immunosuppressants commonly used in kidney transplantation both in the initial phase (de novo) and in the maintenance phase. In addition, today it is considered routine clinical practice in case of side effects mediated by CNI (tacrolimus or cyclosporine) or by antimetabolites (mycophenolate mofetil or mycophenolic acid) to replace the latter with iMtor (conversion to iMtor). Interestingly, recently reported clinical studies have shown a significant decrease in the rate of both CMV infection and disease in patients treated with mTor inhibitors (i-mTOR) after kidney transplantation, both in combination with MPA. as in combination with CNI drugs. A recently published randomized clinical trial that included more than 2000 kidney transplant patients has reported that the incidence of CMV viral infection in the CNI plus everolimus group in the Serology D / R + / + group was 3.6% compared to 13.3% of the control group treated with CNI plus mycophenolate mofetil. (RR 0.27 - CI 0.19-0.38) This effect has been reported mainly among R + / D + patients, and even in those after receiving induction treatment with rATG. Although the mechanism through which i-mTORs can inhibit and block viral replication after transplantation is unknown, it is suggested that it could be through their ability to directly inhibit proliferation on the virus, or well, through some of the immunomodulatory pleiotropic effects that they exert on the adaptive immune response. Along these lines, beyond its immunosuppressive capacity by inhibiting the lymphocyte proliferation signal ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04936971
Study type Interventional
Source Hospital Universitari de Bellvitge
Contact
Status Withdrawn
Phase Phase 4
Start date September 2021
Completion date September 2021

See also
  Status Clinical Trial Phase
Recruiting NCT04910867 - APOL1 Genetic Testing Program for Living Donors N/A
Completed NCT02723591 - To Compare the Effects of Immediate-release Tacrolimus and Astagraf XL on Donor-Specific Antibody (DSA) Formation and the Development of Immune Activation (IA) in de Novo Kidney Transplant Recipients Phase 4
Completed NCT05945511 - Silent Gallbladder Stone in Kidney Transplantation Recipients: Should it be Treated?
Completed NCT02234349 - Bile Acids and Incretins in Pancreas Kidney Transplant Patients N/A
Completed NCT04496401 - PK Study in Diabetic Transplant récipients : From Twice-daily Tacrolimus to Once-daily Extended-release Tacrolimus Phase 4
Recruiting NCT05917795 - Endoscopic Sleeve Gastroplasty With Endomina® for the Treatment of Obesity in Kidney Transplant Candidates N/A
Not yet recruiting NCT05934383 - Safety and Efficacy of Ultrasound Renal Denervation in Kidney Transplantation Patients With Uncontrolled Hypertension N/A
Not yet recruiting NCT04540640 - Oxygenated Machine Preservation in Kidney Transplantation N/A
Not yet recruiting NCT03090828 - Economic Evaluation of an Education Platform for Patients With End-stage Renal Disease N/A
Recruiting NCT02908139 - Noninvasive Perioperative Monitoring of Arterial Stiffness, Volume and Nutritional Status in Stable Renal Transplant Recipients N/A
Terminated NCT02417870 - Ultra-low Dose Subcutaneous IL-2 in Renal Transplantation Phase 1/Phase 2
Completed NCT02560558 - Bela 8 Week Dosing Phase 4
Recruiting NCT02154815 - Pre-emptive Kidney Transplantation Quality of Life N/A
Completed NCT02235571 - iChoose Decision Kidney Aid for End-Stage Renal Disease Patients N/A
Enrolling by invitation NCT01905514 - ImPRoving Adherence to Immunosuppressive Therapy by Mobile Internet Application in Solid Organ Transplant Patients N/A
Completed NCT02147210 - Chronic Transplant Glomerulopathy and Regulation of Expression of Ephrin B1 N/A
Recruiting NCT01699360 - The Biomarker for Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients Phase 4
Completed NCT01672957 - ORANGE Study: An Observational Study on Renal Function in Kidney Transplant Patients on Immunosuppressive Therapy Containing CellCept (Mycophenolate Mofetil) N/A
Completed NCT01655563 - Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation Phase 2
Terminated NCT01436305 - Optimization of NULOJIX® Usage As A Means of Avoiding CNI and Steroids in Renal Transplantation Phase 2