Research Activity Attività di Ricerca >>

The focus of the OSR Transplant Program is to improve transplantation outcomes. Kidney transplantation is the only available cure for end-stage kidney disease; similarly, beta cell replacement (i.e. pancreas or pancreatic islet transplantation) represents the only available therapy to achieve insulin independence in type 1 diabetes. Enhancing patient access to these procedures, when indicated, and preserving organ function after transplantation is pivotal to reduce the burden of end-stage kidney disease and type 1 diabetes. Our clinical research activity relates to different aspects of kidney and pancreas transplantation, with a high specialization in pancreatic islet transplantation. Our Unit is also involved in clinical research projects aimed at understanding and treating the mechanisms underlying the metabolic abnormalities associated with obesity, both in transplant recipients and in the general population.

Research Activity

1. Beta cell replacement (pancreas transplantation, islet transplantation)
Our research aims at identifying the immunosuppressive regimens with the most favorable risk-benefit ratio for patients undergoing beta cell replacement, and the most appropriate site for pancreatic islet transplantation. Furthermore, beta cell replacement allows studying the effect of type 1 diabetes remission on diabetes-related complications (e.g. diabetic nephropathy, retinopathy, diabetic bone disease), which in turn may help improve our understanding of the mechanisms underlying such complications and develop novel strategies to prevent them.

2. Kidney transplantation 
Viral infections may lead to graft loss in kidney transplant recipients. Our Unit participates in multicenter randomized clinical trials to assess the efficacy of novel drugs to tackle cytomegalovirus (CMV) and BK virus infections. Our efforts are also directed at identifying predictors of progression to BK virus-associated nephropathy.

Post-transplantation diabetes (PTDM) is another complication that may severely affect both short- and long-term outcomes of kidney transplant recipients in terms of graft and patient survival. The Unit is developing research protocols to assess the efficacy of prevention strategies as well as the efficacy and safety of different therapeutic approaches to improve metabolic control and long-term outcomes.

Our Unit, in collaboration with the Transplant and Metabolic/Bariatric Surgery Unit, is also assessing the role of hypothermic machine perfusion in the prediction of postoperative kidney transplantation outcomes.

3. Obesity and insulin resistance
Morbid obesity may contraindicate transplant surgery. On the other hand, weight gain and obesity are frequent after organ transplantation, due to several factors including immunosuppressive drugs and psychological factors. The presence of obesity increases risk of PTDM and adverse outcomes in transplant recipients. In collaboration with the Transplant and Metabolic/Bariatric Surgery Unit, our Unit is studying the role of weight loss surgery in the management of kidney transplant candidates and recipients.

Sarcopenic obesity (SO), i.e. obesity with reduced muscle mass/strength, is associated with increased morbidity/mortality and metabolic derangements. In collaboration with the Transplant and Metabolic/Bariatric Surgery Unit, we are developing protocols to dissect the mechanisms underlying SO and identify biomarkers for diagnosing and monitoring the condition.

4. Phase I trials
The Transplant Medicine Unit has been recently certified as Accredited Phase I Research Unit by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA).

Before being used as a drug, an “active ingredient” must be evaluated in preclinical studies (either laboratory or animal studies) and in human studies, which involve 3 subsequent stages:

Phase 1 is the “experimental phase”, where the active ingredient is used in humans. The aim of Phase 1 studies is to assess the safety and tolerability of an active ingredient/drug. If the drug’s toxicity profile is deemed acceptable in light of the expected benefits (risk-benefit profile), the investigational drug moves on to the following steps.

Phase 2 is the “therapeutic-exploratory phase”, which assesses the therapeutic effects of the drug. Furthermore, in this Phase the dose regimen needed to achieve therapeutic efficacy is assessed.

Phase 3 is the therapeutic confirmatory phase, where the efficacy of the new drug is compared to placebo (a substance with no therapeutic efficacy), already available drugs or no treatment.

At the end of Phase 3, if the results indicate that the therapeutic properties of the drug outweigh potential risks, all data is submitted to Regulatory Agencies (Food and Drug Administration, European Medicines Agency) that will review the application and approve the drug for marketing if the data is found worth.

Not all healthcare facilities meet the criteria for hosting clinical (human) trials. Particularly, in 2015 the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) issued the Determination 809/2015 (published in the Gazzetta Ufficiale, issue 158, 10 July 2015) with the minimum requirements for healthcare facilities involved in Phase I clinical trials.

Since 2016 and throughout the course of 2017, the Unit has worked hard in order to meet all the requirements set by the AIFA to be certified as a Phase 1 Facility. To this end, the Unit underwent a formal and structural reorganization, reaching the goal and obtaining the certification in July 2018.
Standard Operating Procedures have been compiled to detail and provide instructions on all the activities relating to the planning and conduct of clinical trials.
Great attention has been given to those aspects related to safety of patients enrolled in a trial, including the management of urgent and emergency situations. Furthermore, all the aspects concerning the requirements about quality of research activities and process tracking have been taken into account (e.g. specimen tracking, from sampling to analysis).
Specific professional profiles (i.e. Director, study coordinator, data manager, research nurse, statistician, physician-investigator) have been identified to address each of the tasks needed to complete such processes. Required qualifications as well as responsibilities, competences, training and maintenance of training requirements have been established for each professional profile. The capability to conduct Phase 1 studies puts the Internal Medicine and Transplantation Unit – HSR among the clinical and research Institutions in an avant-garde position in Italy. This is important not just for scientific aspects but also for clinical and therapeutic aspects, as we can offer innovative therapeutic options to our patients.

Ongoing Clinical Trials

Changes in vaginal pH and microbiome after kidney transplantation, and their effect on the risk of urinary tract infections: a prospective cohort study. Investigator initiated, in collaboration with the Obstetrics and Gynecology Unit, San Raffaele Scientific Institute.

Effect of type 1 diabetes remission by pancreas transplantation alone on fracture risk: a retrospective matched cohort study. Investigator initiated.

MK8228-002 Nº EudraCT: 2017-001055-30
A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of MK-8228 (Letermovir) Versus Valganciclovir for the Prevention of Human Cytomegalovirus (CMV) Disease in Adult Kidney Transplant Recipients

SHP620-303: EudraCT: 2015-004725-13
A Phase 3, Multicenter, Randomized, Open-label, Active-controlled Study to Assess the Efficacy and Safety of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients with Cytomegalovirus (CMV) Infections that are Refractory or Resistant to Treatment with Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir.

Cirrus 1-CCFZ533A2201 EudraCT: 2017-003607-22
A 12 month, partially-blinded, active-controlled, multicenter, randomized study evaluating efficacy, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) of an anti-CD40 monoclonal antibody, CFZ533, in de novo and maintenance kidney transplant recipients (CIRRUS I)

VETRIS Study: Observational, retrospective cohort study in kidney transplant recipients and venous thromboembolism. Sponsor: Arianna Anticoagulation Foundation

Iatrogenic immunosuppression after kidney or liver transplant and virus-related and non-virus related cancers (funded by the Italian Association for Cancer Research (Associazione Italiana per la Ricerca sul Cancro, AIRC)

A multicentre study to detect Cancer in Transplant Patients (funded by the European Regional Development Fund - Operational Programme for the Campania region)




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