Clinical trials

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.

This study is designed as on observational, retrospective, and prospective clinical registry aimed at collecting comprehensive real-world data on women in perimenopause, menopause, and with premature ovarian insufficiency (POI) attending a specialized Menopause Clinic and a Multidisciplinary Outpatient Clinic dedicated to Endocrinology and Metabolic Disorders. The registry comprises both retrospective data, extracted from the medical records of eligible patients evaluated from January 2000 onward, and prospective data, which will be continuously collected for all newly referred patients up to 2040. This combined design allows the longitudinal observation of clinical characteristics, management strategies, and health outcomes across different stages of the menopausal transition and premature ovarian insufficiency within routine clinical practice. Clinical management and therapeutic strategies, including hormone replacement therapy and non-hormonal interventions, will be documented. Laboratory data, as well as imaging data routinely used in clinical practice, will be recorded when available. Enrolled patients will undergo a personalized follow-up schedule based on clinical findings and the conclusions of each visit, in accordance with standard clinical practice. Follow-up visits may be scheduled annually for routine monitoring or at shorter intervals (semi-annual or quarterly) in the presence of conditions requiring closer clinical surveillance. The registry is intended to reflect real-world clinical practice and to support the descriptive evaluation of patterns of care, symptom burden, and longitudinal clinical outcomes in women undergoing the menopausal transition or affected by premature ovarian insufficiency. The collected data will provide a structured platform for epidemiological analyses and hypothesis-generating observational research aimed at improving the understanding and management of menopausal health and associated endocrine and metabolic conditions.

This study explores early breast cancer, focusing on triple-negative and high-risk luminal subtypes. It combines single-cell RNA sequencing and spatial imaging of tumor samples collected at different time points during treatment. The aim is to better understand how cancer cells and immune cells interact and to identify biomarkers that can predict whether a patient will respond to chemo-immunotherapy or develop resistance. The study assumes that early molecular and spatial changes at the single-cell level can predict treatment response. This knowledge could help doctors adapt therapies, avoiding unnecessary treatment while improving effectiveness. The project seeks to reveal, for the first time, how cellular diversity and spatial relationships contribute to treatment resistance and disease progression. Tumor samples will be analyzed before treatment, after the first treatment cycle (C1D1), and at surgery. Only the biopsy taken after C1D1 is collected specifically for this study; all other samples come from routine clinical care.

This is a retrospective study encompassing all \[18F\]FET PET scans performed at our centre. By analysing both static and dynamic scans, conducting in-depth kinetic modelling, and comparing quantitative parameters across different tumour types and clinical contexts, the study aims to determine the true diagnostic value of \[18F\]FET PET in everyday clinical practice. The ultimate goal is to identify imaging biomarkers useful for improving tumour characterisation and distinguishing recurrence from post-treatment changes, thereby strengthening the role of \[18F\]FET PET in modern neuro-oncology.

This is a Single-center, diagnostic open-label prospective, pilot study in a total of 10 patients affected by Prostate cancer (PCa) with a risk of lymph node invasion (LNI) higher than 5% and candidates for a robot-assisted radical prostatectomy (RARP) with an extended pelvic lymph node dissection (ePLND) . The aim of the trial is to evaluate the feasibility and accuracy and clinical value of a novel high-resolution perioperative PET-CT-scan for intraoperative margin and lymph node invasion assessment, after 18F-PSMA injection, using histopathology as the gold standard.

The use of immunomodulants in patients with GI cancer has been progressively gaining attention in the last years, as a high-calorie-high-protein nutritional blend enriched in immunonutrients has shown efficacy in several studies in reducing the risk of post-operative complications and the length of stay of patients undergoing major cancer surgery. The guidelines for the nutritional management of patients with cancer agree on the utility of nutritional support, whenever it is necessary, to improve clinical outcomes, and the efficacy and tolerability of treatments. To our knowledge, this is among the first clinical trial specifically designed to evaluate the role of immunomodulants-enriched ONS in combination with nutritional counseling in reducing serious AEs rate in patients with advanced GI cancers undergoing systemic treatments.

Recent advances in breast surgery, together with the increasing adoption of conservative surgical approaches, have renewed interest in pre-pectoral implant-based breast reconstruction. Within this reconstructive paradigm, surgeons may employ two distinct strategies: (i) immediate reconstruction using a direct-to-implant approach (DTI), or (ii) a two-stage reconstruction consisting of tissue expander placement followed by definitive implant insertion (TE-I). Each approach is associated with specific indications, advantages, and inherent limitations. The EXPRESSO study aims to retrospectively compare surgical outcomes between pre-pectoral DTI and TE-I breast reconstruction. By providing real-world evidence on these reconstructive strategies, this study seeks to inform surgical decision-making and to optimize reconstructive outcomes in contemporary breast cancer care.

This is a multicenter prospective observational study aimed at evaluating the role of an ultrasonographic score in monitoring disease activity in patients with Takayasu arteritis (TAK). Patients with active disease, either at new diagnosis or during relapse, will undergo serial vascular US assessments during follow-up according to routine clinical practice at each participating centers. For each patient, an OMERACT-derived US score (OTUS) will be calculated. This score was developed and preliminarily validated in previous phases of a multistep project endorsed by OMERACT (Outcome Measures in Rheumatology), an international initiative focused on the development and validation of outcome measures in rheumatology. The study hypothesis is that this score is sensitive to change over time and can be used to monitor disease activity and predict outcome in patients with TAK.

The aim of this clinical study is to increase the rate of pathological responses up to 70% by means of improved patient selection operated by a radiobiological index called ERI\_TCP and by an increase in the dose of radiotherapy in the final concomitant boost of preoperative radiochemotherapy treatment for rectal adenocarcinoma.

The goal of this observational study is to investigate the clinical, immunological, and neuromuscular features associated with the development and progression of myasthenia gravis (MG) in adult patients with thymic abnormalities and/or MG-related antibodies, including individuals with or without clinically manifest disease. The main questions it aims to answer are: * Whether integrated clinical, serological, and histopathological profiles are associated with the presence of MG and can predict disease onset or progression * Wheter systemic immune markers are associated with disease activity, progression, and neuromuscular junction alterations Participants will: * Undergo clinical, neurological, and neurophysiological assessments at baseline and during follow-up * Provide blood samples for serological and immunological analyses * Provide thymic tissue and residual intercostal muscle samples (when undergoing clinically indicated thymectomy) for research analyses * Attend follow-up visits at 6, 12, and 18 months * Record daily symptoms using an electronic patient-reported outcome tool (for participants with MG)

Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. Coronary Computed Tomography angiography (CCTA) gained a pivotal clinical role for excellent sensitivity in rule-out CAD, but has limited specificity for a tendency to overestimate stenoses and for the lack of information about their hemodynamic impact. Fractional Flow Reserve derived from CT (FFR-CT) and stress CT perfusion (CTP) have been recently proposed to complement CCTA in the non-invasive assessment of myocardial ischemia, increasing the specificity and avoiding unnecessary catheterization. However, on energy-integrating (EID)-CT, FFR-CT has suboptimal performance, while CTP is affected by high radiation exposure. Both these approaches may benefit by the introduction of the new Photon Counting Detector (PCD)-CT technology, but data completely lacks. Aim of the study is to assess the performance of PCD-CT in the identification of significant CAD combining CCTA with FFR-CT and spectral CTP.

Prospective observational study designed to describe the clinical, laboratory, imaging, microbiological characteristics and treatment of specific infectious diseases, with the addition of a dedicated biobank.

The present research is an observational clinical study. The project aims to investigate astrocytic damage, assessed through biological findings such as an increase in GFAP level and/or MRI water index, in patients with NMOSD and its potential role in predicting demyelinating relapses or affecting disability outcomes. It will also explore predictors of astrocytic relapses, focusing on demographic, clinical, and immunological biomarkers like T cell responses, B cell repopulation, and cytokine levels. The goal is to identify unrecognized disease activity, providing insights for future research and clinical trials. The study will involve 8 sites in Italy: 6 NMOSD clinical centers for patient enrolment and 2 centers for bioengineering and biological analysis. Centralized analysis of the MRI images of all patients enrolled in the clinical centers will be performed by the Neuroimaging Research Unit Fase 1 of San Raffaele Hospital. A total of 50 patients will be included and they will be followed for 12 months. Comprehensive evaluation of patients, including clinical assessment, bioengineering evaluation, MRI, and blood samples, will be conducted at baseline, month 6, and month 12. To assess silent astrocytic relapses, a specialized evaluation will take place at months 3 and 9, including clinical analysis, blood samples to assess biomarkers like GFAP, a reduced MRI protocol to assess MRI water index, and bioengineering evaluation. In the case of a classical relapse, a dedicated visit will occur within 5 days of symptom onset, using the same evaluation protocol as at months 3 and 9 (MRI and biomarkers will be evaluated if not done in the month before).

The study will be conducted as a monocentric observational prospective study design wants to evaluate the prevalence of vertebral fractures in the cohort of patients that perform a chest-abdomen CT for medical indication other than osteometabolic pathologies.

The Endocrinology Unit of the IRCCS San Raffaele Hospital is dedicated to establishing a prospective single-center registry with data from patients undergoing vitamin D supplementation, initiating their first visit to the outpatient unit until December 2029. 1000 patients will be enrolled, aligning with the unit's recent patient influx for hypovitaminosis D. The registry's goal is to assess the epidemiological trend, identify risk factors, and evaluate the diagnostic and therapeutic clinical management strategies for hypovitaminosis D. It will involve collecting clinical, laboratory, and historical data during outpatient visits, adhering to the standard diagnostic and therapeutic protocols for endocrine-metabolic diseases. This data collection is expected to continue for a duration of ten years.

Aim of this work was to assess the role of polymorphisms belonging to genes involved in the regulation of ionic homeostasis in Caucasian patients with Ménière Disease (MD) and compare results with a cohort of patients affected by vestibular migraine and a cohort of non vestibular subjects

Liver metastases (MTS) are the main cause of death for patients affected by colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC), thus representing the major unmet clinical need for these malignancies. Based on preliminary and published data, the investigators hypothesize that innovative immune, gene, and cell therapy approaches might overcome the tolerogenic liver microenvironment and represent powerful therapeutic tools for liver MTS of PDAC and CRC. The investigators have therefore planned an observational clinical study to enroll distinct cohorts of patients (i.e., metastatic CRC, preneoplastic, metastatic, and non-metastatic PDAC) and finely characterize, through integrated state-of-the-art -omics, the immune and non-immune microenvironment of their primary tumor and/or liver metastases as well as correlate changes in the activation status and phenotype of peripheral blood leukocytes. Healthy volunteers will be enrolled as negative controls. The investigators aim at identifying: i) actionable tumor-associated antigens (TAAs) and local immune suppressive and regulatory pathways; ii) biological parameters for early diagnosis of relapse; iii) the effect of therapies on the shaping of anti-tumor immune responses. Data collected will be instrumental for the generation of novel advanced therapy medicinal products (ATMPs). Indeed, this protocol is part of a multi-partner translational program, supported by the AIRC 5 per Mille 2019 grant, focused on the development, validation, and implementation of clinical testing for ATMPs to ameliorate the cure of CRC and PDAC, and possibly to help the study of other solid tumors. Moreover, the systematic and long-term follow-up of enrolled patients will possibly point to early predictors of differential prognosis and patients' categories eligible for tailored therapies, including those with the novel ATMPs. In this regard, two additional substudies were incorporated into the main LiMeT protocol in July 2024 and January 2026, respectively, supported by supplementary funding: 1) the TREATLIVMETS (Treating Liver Metastasis) project, funded by the European Research Council (ERC) under the Horizon Europe research and innovation program; 2) the "Deciphering and targeting the immunological niche in PDAC" project, funded by the Fondazione Regionale per la Ricerca Biomedica (FRRB) under the "From Bed to Bench 2024" call. In the latter substudy, machine learning will be integrated with the spatial multi-omic profiling of the immune landscape in preneoplastic and neoplastic lesions in a subset of IPMN and PDAC patients, supporting the discovery of new therapeutic targets and enabling the early detection of preneoplastic lesion progression.