Clinical trials

Ventral hernia repair is one of the most commonly performed abdominal surgical procedures worldwide, increasingly carried out using minimally invasive techniques. In this setting, mesh reinforcement is standard practice, but the optimal anatomical plane for mesh placement remains debated. Intraperitoneal and extraperitoneal mesh positions may have different long-term consequences, particularly when patients undergo subsequent abdominal surgery. However, prospective data evaluating the impact of prior mesh position on reoperative risk and postoperative outcomes are limited. The ORION study is a prospective, multicentre, observational cohort study designed to evaluate the impact of prior minimally invasive ventral hernia repair with intraperitoneal versus extraperitoneal mesh placement on subsequent minimally invasive abdominal surgery. The primary objective is to compare the incidence of intraoperative visceral injury during adhesiolysis between the two mesh positions. Secondary objectives include the assessment of adhesion burden and severity, duration and extent of adhesiolysis, conversion to open surgery, and adhesion-related postoperative complications. In a predefined subgroup of patients undergoing surgery for ventral hernia recurrence, the study also evaluates short-term postoperative outcomes, including chronic post-surgical pain, neuropathic pain features, sensory disturbances, and analgesic use. By prospectively collecting standardized intraoperative and postoperative data across multiple centres, the ORION study aims to provide real-world evidence on the long-term surgical and functional implications of mesh positioning in minimally invasive ventral hernia repair.

Migraine is the leading cause of disability worldwide among people aged 15 to 49. Although therapies targeting the CGRP pathway have improved the management of the condition, there are large groups of patients who do not respond to medications or for whom these are contraindicated. In this context, non-pharmacological therapies such as physical therapy play a crucial role. The scientific literature highlights a strong link between migraine and cervical disorders: * 77% of migraine patients suffer from neck pain. * 93% have at least three musculoskeletal dysfunctions in the cervical region. * Patients with cervical symptoms experience more frequent attacks, greater disability, a poorer response to medication, and a higher risk of chronicity. Despite the proven utility of physical therapy for the prevention and treatment of migraine (as demonstrated by validated physical tests and standardized questionnaires such as the NDI, HDI, and HIT-6), musculoskeletal screening is not routinely included in neurological examinations. Neurologists in headache centers generally lack the time and specific manual skills required to perform a thorough physical assessment of the cervical spine. There is therefore a lack of a rapid and effective screening tool that serves as a "bridge" between neurology and rehabilitation. The primary objective of the MIGSKA study is to evaluate the performance of the Doraldo-Castelletti scale in assessing the clinical need and motivation of patients with migraine to undergo physical therapy. The study will also assess the utility of this scale as a decision-making tool for neurologists in referring appropriate patients to physical therapists. To address this gap in clinical practice, the study analyzes the Doraldo-Castelletti scale. The adoption of this tool aims to: * Easily identify migraine patients with significant musculoskeletal dysfunction. * Quantify the patient's attitude and motivation toward manual therapy (a determining factor for treatment success). * Provide the neurologist with an objective and rapid criterion for prescribing a specialized physical therapy evaluation, promoting a genuine and effective multidisciplinary approach to migraine care.

Osteoporosis is a systemic skeletal disorder affecting approximately 10% of individuals over 50 years of age. It is characterised by an increased risk of fragility fractures, which constitute a major source of morbidity, mortality, and healthcare burden worldwide. A range of pharmacological therapies has been approved for osteoporosis, with demonstrated efficacy in reducing fracture risk. These include anabolic agents that stimulate osteoblast-mediated bone formation (teriparatide, abaloparatide), antiresorptive agents that inhibit osteoclast-driven bone resorption (bisphosphonates, denosumab), and dual-action agents such as romosozumab, which, through sclerostin inhibition, simultaneously enhances bone formation and suppresses resorption. In clinical practice, these agents are administered sequentially or in combination to optimise therapeutic outcomes. The primary goal of anti-osteoporotic therapy is to reduce the risk of incident and subsequent fractures. In postmenopausal osteoporosis, this objective is closely linked to meaningful gains in bone mineral density (BMD), as measured by dual-energy X-ray absorptiometry (DEXA), with attainment of osteopenic ranges associated with low fracture probability (\<15% for major osteoporotic fractures and \<3% for hip fractures, according to FRAX). However, selecting the most effective therapeutic strategy remains challenging, as robust predictors of individual treatment response are lacking. Although bone turnover markers are widely used to monitor treatment effects, their value in predicting clinical outcomes is limited. MicroRNAs (miRNAs) are small (\~22 nucleotides), single-stranded, non-coding RNAs that regulate gene expression at the post-transcriptional level through binding to complementary sequences in target mRNAs. Circulating miRNAs are stabilised by association with proteins and extracellular vesicles, making them attractive candidates as biomarkers. Increasing evidence indicates that miRNAs play key roles in osteoblast and osteoclast differentiation, proliferation, and apoptosis, and distinct miRNA expression profiles have been associated with osteoporosis and fragility fractures. An emerging area of interest is the interaction between osteoactive therapies and circulating miRNA signatures. To date, available data are largely limited to antiresorptive agents and teriparatide. No studies have yet addressed miRNA expression profiles in patients treated with romosozumab or abaloparatide. Beyond miRNAs, additional molecular pathways implicated in osteoimmunological crosstalk and ageing are gaining attention as potential biomarkers. Nitric oxide (NO) plays a multifaceted role in bone homeostasis, inhibiting osteoclast activity while promoting osteoblast function. Reduced circulating NO levels have been identified as an independent predictor of osteoporotic fractures in postmenopausal women. Autophagy is increasingly recognised as a critical regulator of bone remodelling, influencing both osteoblastic and osteoclastic activity. Dysregulation of autophagic pathways disrupts bone homeostasis and contributes to bone loss. These processes are tightly controlled by complex molecular networks, including miRNAs, and are closely linked to lysosomal function. In this context, cathepsin K has emerged as a promising therapeutic target in osteoporosis. The present study primarily aims to identify circulating microRNAs, whose early treatment-induced changes are predictive of the outcome of the therapy in terms of changes in BMD. Secondary, it aims to identify correlations of the changes in microRNAs serum concentrations with variations in biomarkers of bone metabolism as well as of aging. The study enrols women with diagnosis of severe postmenopausal osteoporosis addressed to treatment with romosozumab or with abaloparatide. All women will be assessed at baseline and after 2, 6 and 12 months of treatment.

Obesity is a significant health problem whose prevalence has tripled worldwide in the last fifty years, also involving older people. Older people present sarcopenia, characterized by the progressive loss of muscle mass and strength. Sarcopenia, accompanied by an increase in adipose tissue, causes a specific condition called sarcopenic obesity. The increase in adipose tissue and the decrease in muscle mass determines a reduction in strength and physical abilities necessary to perform everyday activities of daily living in obese older people. To understand how the condition of excess adipose tissue influences the activities of daily living of older people with obesity, it is necessary to compare the physical abilities, body composition, and results of various motor skills with normal-weight subjects, corrected for sex and age.

The effectiveness of low-protein diets supplemented with essential aminoacid (EAA) formulas in genetic disorders of amino acid (AA) catabolism, such as maple syrup urine disease (MSUD), is widely recognized (Blackburn PR et al. 2017). The main aim of the present study is to evaluate a difference in the effectiveness of a multidisciplinary rehabilitation program in patients with high degree of obesity with and without supplementation of this new formula of amino acids (essential + tricarboxylic acids - EAA-AC). For this reason, patients of both sexes, aged between 45 and 65, suffering from high-grade obesity will be recruited in Piancavallo. The enrolled patients divided, randomly, into two groups will be given: EAA-AC group a low-calorie and low-protein diet integrated with 4 sachets of EAA-AC supplement per day; the control group will follow a low-calorie and low-protein diet only with placebo. The parameters considered, after two weeks of treatment, will be: weight loss; the maintenance/recovery of muscle mass assessed through changes in body composition and functional tests (Hand grip, 6MWT or TUG) but also through the analysis of mitochondrial function in PBMC and circulating levels of mtDNA; the improvement of the glucose picture and the lipid profile. 1 month after discharge, patients will carry out an outpatient check-up to evaluate the maintenance of muscle mass using impedance testing.

Observational prospective single-center, non-profit study. Primary objective of the study: To determine if the hypotensive phenotype, defined as one episode of daytime systolic blood pressure (SBP) \<90 mmHg (or two episodes of daytime SBP \<90 mmHg, if mean 24 h SBP is \<125 mmHg) detected at Ambulatory Blood Pressure Monitoring (ABPM) is associated with adverse events at follow up (death, hospitalization, falls, emergency room admission for uncontrolled hypertension, major cardiovascular events)

Body Mass Index (BMI) is currently the most widely recommended parameter for identifying underweight subjects. Among eating disorder diseases, anorexia nervosa (AN) is the one with the highest mortality rate and with relapses between 12 and 27%. To date, recovery programs allow approximately 40% of subjects to achieve recovery, 30% demonstrate improvements, and 20% remain chronically affected. These data demonstrate the importance of continuously monitoring changes in weight and body composition of these subjects. Bioelectrical impedance (BIA) is widely used to determine body composition in AN. BIA provides various parameters, such as lean mass (LM), fat mass (FM), total body water (TBW), and phase angle (PhA). Among these parameters, in addition to LM and FM, PhA has also been used to characterize underweight subjects with AN. In addition to the observed relationship between PhA and body composition in individuals with AN, PhA has also been related to the basal metabolic rate (BMR). BMR undergoes changes mainly due to loss of muscle mass and a significant reduction in BMR has been observed in AN subjects. Finally, physical activity represents a significant determinant of body composition and can help regulate BMR. Therefore, monitoring changes in body composition (LM, FM, and PhA) and indirect indices (lean mass index and fat mass index) using BIA, together with monitoring changes in BMR and physical activity level, could provide important support for the continuous control and definition of the clinical stage of the disease in patients with AN. The aim of this study is to determine body composition, basal metabolic rate, and level of physical activity in Anorexia Nervosa and normal weight subjects to identify the most consistent parameters to define the clinical stage of the disease in subjects with AN.

: The objective of this research project will be to determine the sphingolipidomic profile in a group of women (\> 18 years) affected by Anorexia Nervosa (AN), phenotypically characterized (restricting \[AN-R\] vs binge-eating purging \[AN-BP\]). Specific questionnaires will be administered for the definition of the severity of the eating disorder and depressive state (suicidality), to which will be added the evaluation of gonadal function (i.e., plasma levels of estradiol/progesterone and use of oral contraceptives). Based on the specific lipidomic profile, which the present research project hopes to characterize, it will be possible to appropriately modify the diet of rehabilitation programs and, in the future, improve the effectiveness of the treatment itself, especially in the long term.

The objectives of this study will be to determine the methylation of the promoter of the Orexin A (OX-A) and B (OX-B) genes in young women (\> 18 years) with Anorexia Nervosa (AN), compared with a control group; and to evaluate the relationship of promoter methylation of the genes for OX-A and OX-B with the severity of the eating disorder, psychiatric comorbidities (in particular, depression), and sleep quality.

The main aim of the present study is to evaluate in a group of adolescents with obesity, hospitalized for a period of integrated metabolic rehabilitation (calorie restriction, aerobic physical activity, psychological counseling, nutritional re-education) lasting 3 weeks, the effects produced from a period of training with vibration stimulation on vibration platforms (Whole Body Vibration Exercise \[WBVE\]) on the resting energy expenditure (REE), assessed through indirect calorimetry. The results will be compared with those obtained in a control group, subjected to integrated metabolic rehabilitation alone. Secondary aims of the study are to evaluate the effects of training with WBVE also on cardiovascular and musculoskeletal parameters, evaluated through specific functional tests, comparing them with those obtained in the control group.

The present study aims to study the presence of metacognitive beliefs in adolescent subjects with eating and nutrition disorders (END) compared with a control group composed of subjects of the same sex and age belonging to the general population.

MASTER study is a 4-year prospective, randomized, open-label, blinded-endpoint study (PROBE) comparing 2 management strategies 1) office BP as a guide to treatment, or 2) 24-hour ABP as a guide to treatment. Study objectives are to investigate whether a management strategy based on out-of-office BP (Ambulatory BP monitoring) versus a management strategy based on office BP measurements is associated with differences in outcome, including cardiovascular and renal intermediate end points at one year; cardiovascular events at 4 years and changes in a number of blood pressure-related variables throughout the study. Patients will be followed-up during the first year focusing on changes in left ventricular mass index (LVMI, co-primary endpoint) and Urinary albumin excretion (UAE, albumin/creatinine ratio, co-primary end-point), and during the whole 48 month period for both changes in LVMI and UAE and events including all-cause mortality, CV morbidity and mortality, cerebral morbidity and mortality.A total of 1240 subjects will be recruited by 30 centers, taking into account a dropout rate of 15% (620 subjects per randomization arm).

Individuals with Amyotrophic Lateral Sclerosis (ALS) carrying the C9orf72 HRE mutation (C9Pos) often exhibit different phenotypic traits compared to other patients (C9Neg), presenting a more aggressive form of the disease, with also a higher frequency of comorbidity with frontotemporal dementia (ALS-FTD) and a greater prevalence of family history of ALS and/or other neurodegenerative diseases. Considering these characteristics (comorbidity with FTD and family history of ALS and/or other neurodegenerative pathologies) as factors that have their importance from an assistance point of view, both C9orf72 patients and their caregivers may have particular needs in several respects, and in this sense this investigation is configured. This survey aims to describe the various aspects related to the care and quality of life of C9orf72 ALS patients and their respective caregivers, with the goal of identifying actionable steps to improve the quality of life for both.

Homonymous visual field defects (HVFDs) after acquired brain injuries affect daily life by impairing reading, navigation, and social activities, often impacting anxiety and depression. Spontaneous recovery is rare. Rehabilitation approaches include restorative treatments, which aim to expand the visual field through the stimulation of the so-called transition zone, and compensatory strategies, such as audio-visual training (AVT), which combines eye movement exercises with synchronized visual and auditory cues to train oculomotor scanning and overcome the visual field loss. Combining AVT with non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS), may enhance recovery by promoting brain plasticity. Early evidence suggests that tDCS applied to the lesioned visual cortex during AVT can speed and stabilize improvements, potentially also restoring parts of the visual field. However, most studies on AVT have focused on chronic patients, whereas several clinical trials and international guidelines indicate that early treatment of HVFDs in the subacute phase can optimally exploit the window of maximal neural plasticity and prevent secondary degenerative processes, thereby maximizing visual recovery. In the present randomized clinical trial, we assess the efficacy of a multisensory audio-visual training (AVT) combined with tDCS in patients with subacute HVFDs after stroke (\<3 months post-lesion). Participants are randomly assigned to two groups: AVT combined with real anodal tDCS applied to the lesioned occipital cortex (Group 1), or AVT combined with sham tDCS (Group 2). The AVT requires participants to orient their gaze toward spatio-temporally congruent, cross-modal audio-visual stimuli (starting from a central fixation) and press a button as quickly as possible upon detecting the visual target. All stimuli are presented on 2mx2m panel embedded with 40 LEDs and loudspeakers (Diana, Casati, Melzi, Marzoli, et al., 2024). The training will be administered for 90 minutes daily over 10 consecutive days. All participants underwent a neuro-ophthalmological evaluation and neuropsychological assessment of visuospatial functions before the beginning of the training (t0), at the end of the training (t1), at 2 months (t2) and after 1 year (t3).

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons, leading to paralysis and death. Despite its uniformly fatal outcome, ALS shows marked clinical heterogeneity with respect to phenotype, progression rate, cognitive involvement, and survival. This heterogeneity limits prognostic accuracy and complicates patient stratification in both clinical practice and research settings. Neurochemical biomarkers have emerged as promising tools to improve diagnosis, prognostication, and understanding of ALS pathophysiology. Among them, neurofilament light chain (NfL) represents the most established biomarker, reflecting axonal degeneration. Additional biomarkers, including glial fibrillary acidic protein (GFAP), phosphorylated tau (p-tau181), and Alzheimer's disease-related markers (Aβ42 and Aβ40), may provide complementary information regarding astroglial activation, motor neuron subtype involvement, and cognitive-behavioral features. However, the phenotypic correlates, longitudinal trajectories, and biological determinants of these biomarkers in ALS are not yet fully understood. The LONELYALS study is an ongoing, monocentric, observational cohort study with a case-control component, designed to investigate the relationships between ALS phenotype and a comprehensive panel of cerebrospinal fluid (CSF) and blood biomarkers. The study will enroll 140 adult patients with ALS and collect longitudinal clinical, neuropsychological, biological, and laboratory data over a follow-up period of up to 36 months. By integrating biomarker measurements with detailed phenotypic characterization, the study aims to clarify biomarker origins, determinants, and prognostic value, and to identify novel CSF biomarkers relevant to ALS.

The goal of this observational study is to develop a questionnaire for measuring swallowing and throat discomfort symptoms in patients with goiter or thyroidectomy, which complies with the model of Rasch and which satisfies the fundamental measurement axioms (e.g., unidimensionality, linearity, generalizability). Developing a scale with such characteristics would provide clinicians and researchers with a reliable tool for assessing the impact of goiter and for measuring the outcomes after surgery. Also, the study will assess the psychological impact of goiter and thyroidectomy, as well as the characteristics of the surgical scar after thyroidectomy. The questionnaire will be developed in the first phase of the study. Items and response categories will be identified through interviews performed with patients affected by goiter or after thyroidectomy. In the following phases of the study, the questionnaire will be administered to patients before and after thyroidectomy.

The SAFE (i.e., Sleep and Activity For Eating disorders) study aims to investigate the characteristics of sleep, daytime activity, and circadian rhythms in a sample of patients with eating disorders-specifically anorexia nervosa, bulimia nervosa, and binge-eating disorder-as well as the relationship between these variables and physiological parameters (i.e., body mass index, hormone levels, blood chemistry parameters) and psychological parameters (i.e., levels of depression and anxiety, body image, eating-disorder symptoms).

The goal of the study is to build a Register accruing data derived from the compilation of the questionnaire about LifeStyle for a population both of adults and of young boys and girls. The investigators are confident that in this way they will be able to expand the database they already have. The investigators will be able to increase the strength of the correlations between LS indices and health indicators. In particular, the investigators will emphasize the relationship between physical activity, stress, and diet quality on one hand, and on the other, they will focus on physiological parameters, like arterial pressure, gluco-lipid profile, and possible pathologies.

The identification of safe and effective strategies for weight loss and long-term maintenance is critical to reduce the alarming prevalence of obesity worldwide and mitigate obesity-associated health risks. Specifically, Binge Eating (BE) and Food Addiction (FA) behaviors are well known causes of failed weight loss and weight regain. The definitions of their clinical phenotypes are currently evolving. Recent evidence suggests that food choices, behavior and reward may be driven also by taste perception. The hypothesis of this study is that subjects with dysfunctional eating behavior have different taste thresholds compared to obese subjects without eating disorders, and that this characteristic influences food choice and eating behavior. Identifying a difference in the taste thresholds between obese with and without eating disorder will allow us to understand why certain individuals over-consume or binge on densely caloric foods and to give them a tailored dietary treatment so as to maintain weight loss for a long time. The Binge eating and Food Addiction is assessed using Binge Eating Scale and Yale Food Addiction Scale 2.0. Subjects with obesity recruited are divided in 4 groups: without eating disorder, with food addiction (FA), with binge eating (BE) and with FA + BE. In these groups sweet and salty taste will be measured with the 3-Alternative-Forced-Choice method.

Bariatric surgery is the ideal therapeutic strategy for patients with severe obesity when lifestyle interventions have failed. Unfortunately, weight recovery after surgery affects one third of patients and is due to several factors, such as recovery of incorrect eating behaviour, reduction of physical activity or hormonal factors. Dilation of gastro-jejunal anastomosis is one of the main causes as it determines reduction of satiety in the patient and consequent increase of the portions of food consumed. In these cases it is necessary to make a review of gastro-jejunal anastomosis and to reduce surgical complications in recent years has been developed a method that allows the execution of sutures through a totally endoscopic way (OverStitch™ Endoscopic Suturing System). Literature studies to assess hunger-satiety in patients undergoing bariatric surgery, suggest that surgery results in weight loss due to a series of changes in gastrointestinal physiology which impact on the feeling of hunger-satiety, and on the modification of the secretion of hormones involved in the regulation of gastric emptying such as the reduction of ghrelin secretion and the increase in postprandial cholecystokinin and GLP-1. There are no data in the literature on satiety in patients in previous bariatric surgery with weight recovery secondary to dilation of the gastro-jejunal anastomosis. There are various methods to assess satiety, most of which are invasive and difficult to perform in routine clinical settings. A recently proposed method to evaluate the perception of satiety and validated on healthy adults, is the Water Load Tests (WLTs). The test consists in making the subject drink a quantity of water until he feels "pleasantly" full. The volume of water ingested is a valid indicator of the subjective feeling of satiety. The aim of yhe study is to assess perceived satiety (measured by Water Load Test) after intervention of Sleeve Gastrectomy or a revision surgery with OverStitch™ Endoscopic Suturing System in obese individuals suitable for bariatric surgery

This project is aimed at advancing neuropsychological diagnostics, enriching and modernizing the panorama of both clinical and forensic psychometric testing. The rapid socio-demographic changes, the developments of neuropsychological semiotics and nosography, as well as the growing applicative specialization of neuropsychological assessment make it necessary to introduce further tools to satisfy the diagnostic requests in clinical contexts and more recently in the forensic field (i.e., tests to be administered remotely; bedside screeners; domain-specific in-depth tests; tools for assessing testamentary capacity). Specifically, the present study aims to: a) develop, calibrate and evaluate the psychometric properties of I and II level clinical and/or forensic neuropsychological tests evaluating instrumental and non-instrumental functions in a sample of neurologically healthy individuals representative of the Italian population ; b) evaluate the cross-sectional and longitudinal clinical usability of the aforementioned tests in clinical samples (patients with neurological and neuropsychiatric pathologies of different etiology).

Paired associative stimulation (PAS) is a non-invasive brain stimulation protocol, where two stimuli (a peripheral and a cortical one, the latter delivered with transcranial magnetic stimulation - TMS) are repeatedly associated to enhance plasticity in the brain. In the present study, a new cross-modal, visuo-motor PAS protocol - called "mirror-PAS"- will be tested as a possible non-invasive brain stimulation treatment in neurological rehabilitation to promote motor recovery and pain reduction. Participants will perform the standard PAS targeting the motor system and the recently developed mirror-PAS in two separate sessions. The investigators will compare the possible effect of the protocols in terms of neurophysiological and behavioral outcomes to identify the optimal PAS method to enhance plasticity and promote sensory-motor function.

The study aims to determine which method of vagal ganglia ablation is most effective in preventing recurrences of reflex asystole syncope. Currently, some centers perform ablation only in the right atrium, others in both atria (biatrial). There are no comparative studies between the two procedures

This observational study aims to evaluate multiple dimensions of health in patients with Obstructive Sleep Apnea Syndrome (OSAS), before and after three weeks of ventilotherapy. Specifically, the study aims to identify pre- vs post-treatment differences in the following domains: * cognitive performance * blood expression of biomarkers related to neurodegeneration * psychosocial wellbeing Thus, patients will complete the following evaluations before (T0) and after (T1) ventilotherapy: * neuropsychological standard assessment * blood sampling * psychosocial self-reported questionnaires

The goal of this observational study is to learn about the neurological and cardiological phenotype of patients with resistance to thyroid hormone (RTH) syndromes beta and alpha (RTHß and RTHa) due to dominant negative variants in the genes encoding the thyroid hormone receptors alpha (THRA) and beta (THRB). The main question\[s\] it aims to answer are: * Define frequency and improve early diagnosis for RTH syndromes * Developing tools to accelerate diagnosis of RTH syndromes * Development and validation of monitoring tools Participants, recruited at neonatal screening or from cohorts of patients with unexplained specific neuro-cognitive or cardiovascular phenotypes will be submitted to biochemical and genetic investigations. In addition pluripotent stem cells will be generated from peripheral blood cells of RTHs patients and studied in vitro to understand the molecular mechanisms underlying neurological and cardiovascular consequences. In vitro and clinical data, will be correlated to identify biomarkers for monitoring treatment.