Clinical trials

This prospective observational registry aims to systematically collect preoperative, intraoperative, and postoperative clinical data from patients undergoing surgery for benign gynecological conditions. The main goal is to evaluate clinical outcomes, surgical approaches, and complications in real-world clinical practice.

The REACT study is a prospective, single-center, single-cohort study designed to evaluate the feasibility of a 4-week intensive multimodal postoperative rehabilitation program in patients who develop severe complications after proximal pancreatic resection (pancreatoduodenectomy or total pancreatectomy). Postoperative complications after pancreatic surgery may result in substantial physiological and metabolic stress, leading to loss of muscle mass, malnutrition, reduced functional capacity, and delayed recovery. Although prehabilitation programs have been proposed to improve patients' functional capacity before surgery, evidence regarding structured multimodal rehabilitation after pancreatic surgery is currently lacking. Adult patients undergoing elective proximal pancreatic resection who develop a severe postoperative complication (Comprehensive Complication Index \>21) will be eligible for the study. Participants will undergo a 4-week multimodal rehabilitation program starting after hospital discharge and including individualized exercise training, nutritional therapy, and anxiety-reducing techniques. The program may be delivered either in a supervised hospital-based setting or through a home-based program according to patient preference and availability. The primary objective is to assess the feasibility of the rehabilitation program in terms of recruitment, adherence, completion of outcome assessments, completeness of data, and safety. Secondary objectives include evaluating postoperative functional recovery using PROMIS-29 Physical and Mental Health Summary Scores, the 6-minute walk test, and the Duke Activity Status Index. In patients with malignancy who are candidates for adjuvant treatment, return to intended oncologic treatment will also be evaluated. A total of 40 patients will be enrolled and followed for up to 90 days after surgery.

This prospective observational study aims to investigate pathogenic myelopoiesis in patients with pancreatic ductal adenocarcinoma (PDAC) and to characterize the systemic immune alterations associated with tumor-related inflammation. The study will enroll 50 patients with newly diagnosed, non-metastatic, treatment-naïve PDAC and 50 age-matched control patients with intraductal papillary mucinous neoplasm (IPMN) under surveillance and no evidence of pancreatic malignancy. Control patients will be matched to PDAC patients by age within a range of ±5 years whenever feasible. A single peripheral blood sample will be collected at baseline from all participants. In PDAC patients, blood collection will be performed before initiation of any anti-tumor treatment. Translational analyses will characterize circulating myeloid cells, progenitor cells, and hematopoietic stem and progenitor cell-related transcriptional programs using high-dimensional flow cytometry and single-cell transcriptomic analyses. The primary objective is to identify the molecular drivers of pathogenic myelopoiesis in PDAC by assessing quantitative and qualitative differences between PDAC patients and age-matched controls in circulating myeloid and progenitor cell populations and their transcriptional profiles. The study will specifically explore the hypothesis that IL-1β-associated tumor inflammation contributes to systemic reprogramming of hematopoietic progenitor compartments and promotes myeloid-biased hematopoiesis. PDAC patients will also be followed clinically for 12 months using data derived from routine clinical practice to explore associations between baseline pathogenic myelopoiesis-related profiles and subsequent clinical outcomes. No follow-up is required for control patients.

Adult patients with chronic lymphocytic leukemia (CLL), splenic marginal-zone lymphoma (SMZL) and hairy cell leukemia (HCL) followed at participating clinical sites will be enrolled and undergo sampling of additional amount of blood during the blood draws performed as part of standard clinical care. The project aims to develop and validate innovative patient-derived 3D bioprinted models that faithfully reproduce the key microenvironments of lymphoid tissues, enabling a more physiologically relevant study of mature B-cell malignancies.

This is a monocentric, retrospective and prospective study aimed to underline the potential of T-cell receptor (TCR)-mediated Ab recognition from the post transplant setting in acute myeloid leukemia (AML). The study is based on three key biological concepts: * the essential role of CD4+ T cells in leukemia immunosurveillance, * the impact of human leukocyte antigen (HLA) loss or downregulation on immune escape, * the ability of leukemic cells to remodel the tumor microenvironment and impair T-cell function. By addressing these mechanisms, the study aims to identify novel TCRs and generate next-generation engineered T-cell products with improved anti-leukemic activity. The study will be conducted using samples from healthy donors and patients with AML. The Retrospective part will involve samples collected per standard of care from patients already present in the institutional Hematologic Cancer Biobank, while prospective part will regard the use of samples collected during the study protocol from healthy donor and AML patients. Healthy donor peripheral blood samples will be used to isolate tumor-specific TCRs and generate engineered T cells, whereas bone marrow and peripheral blood samples from AML patients will be used to evaluate the anti-tumor activity of the engineered T cells.

Patients with chronic lymphocytic leukemia (CLL) followed at Strategic Research Program on CLL will be enrolled and undergo sampling of additional amount of blood at the time of standard blood tests. Leukemic B cells and peripheral blood mononuclear cells (PBMC).

This is a monocentric, no-profit, retrospective and prospective observational cohort study conducted at IRCCS Ospedale San Raffaele. The study does not entail any additional procedures or interventions for participants. Biological samples (including blood/serum and muscle biopsies) are obtained for a previously approved study (LAMA2\_GUP24002) and collected under the existing BancaINSpe informed consent. For the present study, analyses will be performed on biospecimens already stored or that will be stored at BancaINSpe, using portions of material already collected for the LAMA2\_GUP24002 protocol.

Telemedicine has developed rapidly during the COVID-19 pandemic and is now integrated into the clinical practice of many hospitals. Telemedicine offers many advantages, and even after the end of the pandemic, many patients still choose to undergo healthcare visits remotely. However, the rapid expansion of telemedicine may be associated with the risk of providing patients with unvalidated and uncontrolled telehealth solutions, potentially negatively impacting their health. In this study, the researchers aim to investigate the effectiveness of remote cognitive training in patients with mild-to-moderate Alzheimer's disease (AD) using tablets equipped with virtual reality-based cognitive exercises. The investigators also aim to evaluate the impact of online supervision of cognitive training by a neuropsychologist and to compare the costs and burden of home-based versus hospital-based cognitive training in patients with AD. This project will define the optimal modalities for cognitive telerehabilitation to ensure validated protocols for the continuity of care in AD.

Pediatric refractory Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, not responsive to current treatments. Since hematopoietic stem and progenitor cells (HSPCs) in the bone marrow display immunomodulatory functions and IL-10-producing regulatory cells regulate gut homeostasis, by combining state-of-the-art strategies for the ex-vivo manipulation and expansion of HSPCs and gene delivery systems to drive HLA-class II-restricted antigen presentation and expression of tolerogenic molecules, the investigators propose to dissect the antigen- (Ag-) presenting capacity of HSPCs and to exploit their tolerogenic potential to induce IL-10-mediated tolerance in the intestinal mucosa of IBD patients. The investigators hypothesize that HSPCs can be engineered using commensal-derived Ags w/wo IL-10 to drive the differentiation of Tr1 cells with the desired Ag-specificity to control intestinal inflammation in IBD. The results of this study will pave the way for defining innovative cell-based approaches for treating refractory pediatric IBD.

OCt.IN.N is a national, monocentric, prospective, observational cohort study evaluating the utility and applicability of Optical Coherence Tomography (OCT) in the diagnostic workup and longitudinal monitoring of neurological diseases. 840 patients with Central Nervous System neurological diseases (Multiple Sclerosis, Alzheimer's disease, Parkinson's disease, migraine/headache) and 210 age-matched healthy controls will undergo OCT examination at baseline and at 6, 12, 18, and 24 months of follow-up at IRCCS San Raffaele Hospital, Milan, Italy. OCT is a non-invasive, rapid, and reproducible technique that automatically measures the thickness of individual retinal layers. Retinal layer thicknesses and their longitudinal changes will be correlated with established clinical scales, neuroimaging, and biological markers used in routine neurological practice.

BLAD is a prospective, monocentric, observational epidemiological study with an additional procedure (annual blood draw) evaluating the diagnostic and prognostic performance of plasma biomarkers for Alzheimer's disease (AD) in a large cohort of patients attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital, Milan, Italy. 2000 patients will be enrolled and followed annually for 5 years. A validation sub-study (150 patients) will compare plasma biomarkers against CSF biomarkers as the gold standard. The study aims to establish plasma biomarkers as a less invasive and more cost-effective alternative to CSF analysis and amyloid-PET for the diagnosis and prognosis of AD.

This is a Retrospective and Prospective Observational Single-Center Study. The purpose is to collect all data to generate a registry of primary liver cancer (hepatocellular carcinoma and biliary tract carcinoma) of patients accessing to San Raffaele Hospital. An additional purpose is to identify novel biomarkers to better manage primary liver cancer patients, for whom additional biological samples will be collected. A total of 4000 patients will be enrolled; for the prospective cohort: from protocol approval to the achievement of the last planned patients in the prospective cohort (2000 patients). The retrospective cohort will start from the year 2000. Patients will be followed for 5 years of follow-up.

Type 1 Diabetes is an autoimmune disease in which immune cells contribute to the destruction of insulin-producing pancreatic beta cells. This study investigates whether targeting glucose transporter 1 (GLUT1), a transporter involved in immune cell metabolism, may help modulate autoimmune responses associated with Type 1 Diabetes. The study uses previously collected and biobanked peripheral blood mononuclear cells (PBMCs) from individuals with Type 1 Diabetes. No additional visits, blood draws, or study-specific procedures will be performed on human participants.

This retrospective-prospective study aims to identify the diagnostic parameters most predictive of BSCVA in patients with OSD. Clinical, structural, and biochemical data will be collected from standard-of-care examinations and patient-reported outcome questionnaires. The goal is to determine the most informative biomarkers for visual prognosis, streamline diagnostic workflows, and support individualized management of OSD.

This is a post-market clinical investigation evaluating the effect of immersive virtual reality (VR) as an adjunct to standard local anesthesia during transperineal prostate biopsy. Transperineal prostate biopsy under local anesthesia is commonly associated with patient anxiety, procedural discomfort, and vasovagal reactions, which may negatively impact patient experience and procedural tolerability. Non-pharmacological distraction techniques such as immersive VR have shown potential to reduce perceived pain and anxiety during short, invasive medical procedures by modulating cognitive attention and emotional response. This study investigates whether the use of an immersive VR headset, added to standard local anesthesia, can reduce peri-procedural anxiety and pain compared to standard care alone. The intervention is designed to provide continuous audiovisual immersive distraction starting shortly before the procedure and continuing throughout the biopsy, without altering standard clinical workflow or increasing procedural invasiveness. This is a randomized, controlled, parallel-group, 1:1 superiority trial with a single-blind (assessor-blinded) design. Participants undergoing transperineal prostate biopsy under local anesthesia will be randomly assigned to one of two groups: standard local anesthesia alone (control arm) or standard local anesthesia plus immersive VR (experimental arm). The primary objective is to evaluate whether immersive VR reduces peri-procedural anxiety and pain compared with standard local anesthesia alone. Secondary objectives may include evaluation of patient satisfaction, tolerability of the VR intervention, and incidence of vasovagal reactions or procedural interruptions. The study aims to generate evidence on the feasibility and clinical benefit of integrating immersive VR as a non-pharmacological supportive tool in urological diagnostic procedures.

This is a single-centre, cross-sectional observational study with adjunctive procedure for the healthy voluteers at IRCCS Ospedale San Raffaele's Rehabilitation Department. Patients (n=50): use of inertial measurement units (IMU) and electromyographic (EMG) data routinely acquired during their standard clinical gait-rehabilitation sessions (no protocol changes; purely observational, data extracted from treatments). Healthy volunteers (n=50): age- and sex-matched volunteers who complete three 18 meters gait sessions with IMUs on trunk, thighs, shanks and feet and surface EMG on gluteus, quadriceps, hamstrings, tibialis anterior, and gastrocnemius. Healthy volunteers will be enrolled from hospital personnel, family members of the patients in visit at San Raffaele Hospital. Data \& Analysis: Kinematic (range of motion - ROM, step timing, walking speed) and EMG (activation amplitude/timing) parameters will be extracted. Between-group comparisons will employ t-tests/analysis of variance - ANOVA - (or non-parametric equivalents).

This interventional, single-center, open-label randomized clinical study evaluates the efficacy of an oral dietary supplement (Pervistop®) in women with persistent Human Papillomavirus (HPV) infection. The supplement is a combination of four natural molecules: Epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12 (B12), and hyaluronic acid (HA).The primary objective is to describe the effect of this association on HPV DNA integration into the host genome by measuring the clearance rate of viral oncoproteins E6 and E7. A total of 42 women aged 25 or older with persistent HPV infection and low-grade cervical lesions will be randomized 1:1 into two groups. The treated group will receive one tablet of Pervistop® daily for six months, while the control group will follow standard clinical practice. The study aims to determine if this nutritional intervention can counteract viral persistence.

Single-center, cross-sectional observational study assessing the feasibility of advanced accelerated MRI sequences versus standard ones in terms of image quality, diagnostic reliability, and acquisition time.

This retrospective observational study will evaluate the clinical response to Sterify Gel, a sterile mucoadhesive polymeric hydrogel, when used as an adjunct to non-surgical periodontal therapy in adult patients with stage II, III, or IV periodontitis. The study will analyze already existing anonymized clinical records from patients treated at the Periodontal Unit of IRCCS Ospedale San Raffaele in Milan, Italy. Patients included in the analysis received scaling and root planing/minimally invasive non-surgical periodontal therapy, followed by local application of Sterify Gel into periodontal pockets with probing depth greater than 4 mm. The main objective is to assess reduction in periodontal pocket depth from baseline to 6, 12, and 24 weeks. Other periodontal clinical parameters, including clinical attachment level, gingival recession, bleeding, plaque score, tooth mobility, and furcation involvement, will also be evaluated.

This prospective in vitro study aims to evaluate the effects of two chlorhexidine-based mouthwash formulations on the survival and function of human gingival fibroblasts (hGFs). Gingival fibroblasts obtained from discarded gingival tissue collected during routine dental procedures will be cultured and exposed to different concentrations of a conventional 0.2% chlorhexidine mouthwash and a 0.2% chlorhexidine mouthwash supplemented with N-acetylcysteine (NAC) and hyaluronic acid (HA). Cell viability, apoptosis, migration, and gene expression will be assessed at multiple time points using Trypan Blue exclusion assay, fluorescence-activated cell sorting (FACS), scratch assay, and quantitative real-time PCR. The study is designed to investigate the concentration-dependent effects of chlorhexidine on fibroblast viability and wound-healing-related functions and to determine whether the addition of NAC and HA may improve the biological compatibility of chlorhexidine-based formulations.

The goal of this observational study is to identify newborns at increased genetic risk of developing type 1 diabetes-specific beta-cell autoantibodies in order to determine eligibility for participation in primary prevention randomized controlled trials aimed at preventing beta-cell autoimmunity.

Monocentric retrospective and prospective observational study of patients with colorectal cancer

AHEAD is a prospective, longitudinal, risk-stratified single-arm interventional study enrolling 300 patients with Subjective Cognitive Decline (SCD) at IRCCS San Raffaele Hospital, Milan, Italy. The study uses artificial intelligence (AI) to integrate multimodal data - including MRI, EEG, Optical Coherence Tomography (OCT), neuropsychological assessments, and plasma biomarkers - to identify individuals with underlying Alzheimer's disease (AD) biology and predict cognitive progression. Only participants found to be AD plasma biomarker positive (SCD+) undergo longitudinal follow-up at 12 and 24 months. Participants classified as high risk additionally receive a 6-month personalized multidisciplinary intervention combining high-frequency transcranial magnetic stimulation (TMS), digital cognitive training, structured physical exercise, and targeted management of modifiable vascular and behavioral risk factors.

Classic congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder caused by a defect in the enzyme cascade regulating adrenal steroidogenesis; in approximately 95% of cases the defect is located in CYP21A2, the gene encoding 21-hydroxylase, and is characterized by defective adrenal steroidogenesis and cortisol deficiency. Due to the loss of physiological cortisol feedback on the hypothalamus and pituitary corticotropic cells, ACTH secretion is increased. This results in the accumulation of 17-hydroxyprogesterone (17OHP) proximal to the enzymatic defect in steroidogenesis, which in turn stimulates overproduction of the adrenal androgen precursor androstenedione and adrenal hyperplasia. Treatment of CAH is tailored to the patient and disease severity, aiming to replace cortisol and aldosterone deficiencies while controlling androgen excess and avoiding glucocorticoid overtreatment. Immediate-release hydrocortisone administered multiple times daily remains the recommended first-line treatment in growing children, whereas adult patients are frequently treated with hydrocortisone, prednisone, prednisolone or dexamethasone. However, conventional glucocorticoid regimens cannot adequately reproduce the physiological circadian rhythm of cortisol secretion. In physiological conditions, ACTH-driven cortisol secretion follows a clear circadian rhythm characterized by low evening levels, nocturnal increase between 2:00 and 4:00 a.m., a morning peak upon awakening, and progressive decline during daytime. Dual daytime dosing of immediate-release hydrocortisone in CAH can control ACTH-driven adrenal androgen secretion during the day; however, because of its rapid absorption into the bloodstream and short half-life, the evening dose of hydrocortisone cannot adequately suppress the nocturnal ACTH surge and ACTH-driven adrenal androgen overproduction. Consequently, patients are often exposed to supraphysiological glucocorticoid doses during nighttime hours in an attempt to control morning hyperandrogenism. The disruption of physiological cortisol homeostasis contributes to poor cardiometabolic profile, obesity, insulin resistance, impaired fertility, reduced quality of life, and increased cardiovascular morbidity and mortality observed in patients with CAH. Bone health may also be impaired in patients with CAH because of chronic glucocorticoid exposure and androgen imbalance. Previous studies demonstrated reduced lumbar and femoral bone mineral density and increased fracture risk in both male and female patients. Modified-release hydrocortisone (MR-HC; Efmody®) is a multiparticulate formulation developed to better reproduce physiological cortisol circadian rhythm through chronotherapy. Previous phase II and phase III studies demonstrated improved biochemical control, reduction in androgen excess, lower glucocorticoid exposure, improved fertility outcomes, and sustained long-term efficacy compared with conventional glucocorticoid regimens. However, real-world longitudinal data regarding long-term biochemical, metabolic, cardiovascular, reproductive and skeletal outcomes remain limited, particularly in adult patients transitioning from pediatric to adult endocrine care. The present study is a single-center, retrospective and prospective, longitudinal, open-label observational cohort study aimed at evaluating the long-term real-world outcomes of chronotherapy with modified-release hydrocortisone in adult patients with genetically confirmed 21-hydroxylase deficiency CAH. Retrospective clinical, biochemical and radiological data already available from routine clinical care will be collected from medical records, while prospective observational follow-up will continue according to routine endocrine clinical practice.

This is a prospective single-center observational study comparing single-port (SP) and multi-port (MP) robot-assisted surgery in adult patients undergoing robot-assisted radical prostatectomy (RARP) or robot-assisted partial nephrectomy (RAPN) for prostate or kidney cancer. Consecutive eligible patients will be managed according to routine clinical practice and assigned to SP or MP surgery based on predefined clinical and anatomical criteria, surgeon assessment, patient and tumor characteristics, platform availability, and surgical expertise. No randomization will be performed. The study aims to compare perioperative outcomes between the two surgical approaches, with length of hospital stay (LOS) as the primary endpoint. Secondary endpoints include intraoperative outcomes (operative time, estimated blood loss, and intraoperative complications), postoperative recovery, pain, postoperative complications, readmission rates, positive surgical margins, and hospital costs. Functional and patient-reported outcomes will also be evaluated, including urinary continence, sexual function, health-related quality of life, renal function after partial nephrectomy, decision regret, and cosmetic satisfaction.