Clinical trials

This 2x2 factorial, randomized, controlled pilot study aims to identify a specific microbiota pattern, which could constitute a biomarker of Parkinson's disease, and to evaluate whether specific pathotypes can be associated with different stages of the disease; furthermore, the investigators are committed to evaluating how and to what extent the changes induced by a personalized nutritional intervention combined with physical exercise affect the symptoms and quality of life of patients.

The AIDE/OBS study is a multicenter, observational, non-interventional study designed to collect standardized clinical, radiological, intraoperative visual, and surgical reasoning data from adult patients undergoing non-elective surgery for complicated acute diverticulitis. The study focuses on patients requiring urgent or emergency operative management, including cases following failure of non-operative management. The main intraoperative decision of interest is the choice between sigmoid resection with primary anastomosis, with or without diverting stoma, and Hartmann's procedure. The current phase aims to build a structured multimodal dataset and to validate and refine a preliminary expert-informed decision-support tool. The study does not modify standard clinical practice, surgical indication, operative strategy, or postoperative management. All treatment decisions remain at the discretion of the treating surgical team according to local practice.

Approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) starting in 2018, anti-CGRP monoclonal antibodies (anti-CGRP mAbs) represent the first true revolution in the preventive treatment of migraine due to their selectivity and specificity. To date, four anti-CGRP mAbs have been developed for the preventive treatment of migraine: eptinezumab, erenumab, fremanezumab, and galcanezumab.Anti-CGRP mAbs constitute not only the first specific and selective treatment for the prevention of migraine but also the most extensively studied pharmacological category in this field, considering the vast and complex populations examined. The clinical effects of the various mAbs are substantially comparable and are characterized by several fundamental aspects: * High efficacy in both episodic and chronic migraine, with the presence of super-responders who experience a reduction in the average monthly number of migraine days of \>75% (or even 100%) compared to before treatment. * Efficacy that is independent of the clinical form of migraine - with or without aura - and regardless of whether there is analgesic overuse. * Efficacy maintained even in the presence of depressive or anxious comorbidities. * Rapid onset of action (even more pronounced with eptinezumab), with the therapeutic effect appearing within the first week in most cases. * Excellent tolerability with an absence of class-specific adverse events. * Outstanding treatment adherence and a very low rate of treatment discontinuation in the long term. It should also be noted that the development of anti-drug antibodies or neutralizing antibodies to anti-CGRP mAbs is rare and does not significantly impact the efficacy or tolerability of treatment. Future clinical practice will need to clarify several additional aspects, such as: 1) whether treatment with anti-CGRP mAbs can modify the course of migraine; 2) the appropriate approach regarding any traditional preventive treatment (whether to continue or discontinue it); 3) the definition of the characteristics of non-responders; 4) the definition of patients with a delayed response to treatment. Gepants are oral antagonists of the CGRP receptor. Among the four gepants synthesized so far (atogepant, rimegepant, ubrogepant, zavegepant), atogepant and rimegepant are currently available in Italy. Atogepant has proven to be an effective and well-tolerated option for the prevention of episodic and chronic migraines. Rimegepant is effective for both acute treatment and prevention of migraines, with a favorable safety profile and flexible oral administration. Lasmiditan is the first ditan effective for migraine attack and it represents a new therapeutic option for patients with contraindications to triptans, due to the presence of vascular risk factors, or for patients who experience undesirable side effects with these, thus increasing the therapeutic possibilities for the symptomatic treatment of migraine. The combination of sumatriptan 85 mg and naproxen sodium 500 mg is indicated for the acute treatment of migraine attacks in adult patients for whom sumatriptan monotherapy is insufficient.

This pilot feasibility study will evaluate a wearable soft elbow exosuit and a haptic forearm bracelet for upper-limb neurorehabilitation in people with stroke and Parkinson's disease. The soft elbow exosuit is designed to assist elbow flexion and extension during functional motor tasks while preserving comfort and natural movement, with the possibility of deploying vibrotactile stimuli. The haptic bracelet provides tactile and vibrotactile feedback to support sensorimotor engagement, movement guidance, and proprioceptive awareness. The study will assess the feasibility, usability, comfort, acceptability, safety, and preliminary clinical impact of these devices in a real neurorehabilitation setting. Participants with stroke will be tested using either the soft elbow exosuit or the haptic bracelet, depending on their stage of recovery and residual upper-limb motor function. Participants with Parkinson's disease will be tested with the soft elbow exosuit combined with integrated haptic feedback, with specific interest in motor performance and tremor modulation. Participants will undergo baseline clinical and functional assessment, followed by supervised experimental sessions involving upper-limb functional tasks such as reaching, grasping, releasing, pick-and-place exercises, elbow flexion-extension, forearm pronation-supination, and fine or gross motor activities. Sessions may be performed with and without device assistance. Non-invasive sensors, including inertial measurement units and electromyography, will be used to collect movement and muscle activity data. User experience will be assessed using standardized questionnaires addressing usability, satisfaction, perceived benefit, comfort, and musculoskeletal discomfort. The study is intended to generate preliminary evidence on the safe and acceptable use of wearable soft robotic and haptic technologies in neurological rehabilitation and to inform the design of future larger clinical trials.

This multicenter international randomized controlled trial (RCT) evaluates the effectiveness of the Gloreha Sinfonia® robotic exoskeleton for upper limb rehabilitation in individuals with subacute post-stroke paresis. The study aims to determine whether robotic-assisted therapy improves voluntary motor control and coordination more effectively than conventional rehabilitation, as measured by the Fugl-Meyer Assessment (FMA) for the upper limb (motor component). Participants will be randomly assigned to one of two groups: * Experimental Group (EG): Robotic-assisted upper limb rehabilitation combined with conventional therapy. * Control Group (CG): Conventional therapy alone including upper limb rehabilitation. Clinical assessments will be conducted at baseline (T1), post-treatment (T2), and at a 3-month follow-up (T3) using remotely administered scales. Secondary objectives include evaluating improvements in muscle strength, range of motion, eye-hand coordination, manual dexterity, and functional independence. The study will also assess prognostic factors influencing response to robotic therapy, patient satisfaction, and potential adverse events.

Children with autism spectrum disorder (ASD) often show motor abnormalities and sleep disturbances that affect behavior, learning, and family quality of life. Emerging technologies such as wearable devices and markerless systems provide accessible tools for gait and sleep assessment, with actigraphy recommended for long-term monitoring in natural settings. Evidence also suggests links between sleep problems and sensory processing differences. This project, aims to integrate these approaches in a clinical-translational framework.

Aging is the inevitable biological process that results in a progressive structural and functional decline from the cellular level to whole body function. It is associated with functional changes in the resting brain activity, brain morphology, plasticity, complexity and function. Moreover, aging is the main risk factor for neurodegenerative disease. Understanding the molecular mechanisms underlying the age-related neurophysiological changes and identifying novel biomarkers of healthy brain ageing is thus instrumental for the development of efficient interventions against age-related motor/cognitive impairments. Within this context, there is now a significant literature establishing the enhanced efficacy of secreted exosomes over the stem cells from which they are derived when used as a possible treatment for neurodegenerative disorders. Exosomes are a subgroup of extracellular vesicles which regulate intercellular communication and, unlike stem cells, easily cross into the brain and can be administered in non-syngeneic species without immune rejection. Studies on brain ageing in humans has major limitation in the lack of accessibility of the central nervous system. EEG has allowed the non-invasive assessment of functional changes in the aging brain. In fact, this technique can provide a direct assessment of neural activity and information flow with a higher temporal resolution that is particularly important for investigating the dynamics of brain changes underlying cognitive processing and age-related changes, providing novel biomarkers of brain aging that could be used to unveil differences between healthy and unhealthy processes particularly in the pre-symptomatic and pre-clinical stage. To reach this aim, it is necessary to demonstrate, in experimental models, the relationship between age-dependent changes in brain activity and cellular/molecular processes occurring in aged brain. Our project will pursue this overall goal by: 1\) identifying neurophysiological biomarkers of brain aging in human subjects based on functional network and complexity analyses; 2) characterizing age-dependent changes in brain connectivity and complexity in mice and correlating them to changes in motor and cognitive performances and to molecular alterations occurring in both the brain and blood; 3) evaluating changes of the identified electrophysiological and molecular biomarkers in mice treated with stem cell derived exosomes for the rejuvenation of the aged brain. 4\) designing Artificial Intelligence (AI) predictor of brain age trajectories on individual basis to evaluate individual neural reserve and resilience. This study will identify novel electrophysiological biomarkers of healthy brain ageing and will advance knowledge on cellular/molecular signature of brain aging that could targeted for the preservation of brain health.

Pediatric Feeding Disorders (PFDs) are conditions characterized by persistent difficulties in food intake, commonly manifesting as food selectivity, food refusal, and dysfunctional mealtime behaviors. Their prevalence in the general pediatric population ranges from 3% to 10%, with substantially higher rates reported among children with neurodevelopmental disorders. The impact of PFDs extends beyond growth and nutritional status, affecting cognitive and emotional development as well as the well-being of the entire family system. Although several treatment models have been proposed, scientific evidence supporting outpatient interventions remains limited and Italy-specific studies are lacking. Moreover, despite the availability of standardized assessment tools, feeding-related outcomes are not yet systematically addressed within outpatient clinical practice for children with neurodevelopmental disorders. The present study aims to evaluate whether an interdisciplinary intervention protocol involving a psychologist, a speech and language therapist (SLP), and a Neuro and Psychomotor Therapist of Developmental Age (TNPEE) can improve food variety and reduce dysfunctional mealtime behaviors in this population. The study is designed as a pilot randomized controlled trial developed across five sequential phases: participant enrollment and screening using the Montreal Children's Hospital Feeding Scale (MCH-FS); baseline standardized assessment (T0) using the Pediatric Eating Assessment Tool (PediEAT) and the Short Sensory Profile (SSP); random allocation of participants to an experimental group or a control group; delivery of the interdisciplinary intervention exclusively to the experimental group; and a final standardized assessment conducted six weeks later (T1) to evaluate changes over time and between groups. This pilot study primarily aims to assess feasibility and to estimate the variability of outcome measures; therefore, no formal sample size or power calculation was performed. The planned enrollment of 12 participants per group was determined based on feasibility considerations and in line with CONSORT recommendations for pilot trials. The proposed protocol seeks to address current gaps in the literature by systematically targeting feeding-related outcomes through an explicitly interdisciplinary approach that integrates psychological, speech and language, and neuropsychomotor perspectives in the management of PFD.

Rationale Understanding the mechanisms and evolution of migraine is hampered by its nature as a chronic "evolutionary" condition. Patients often come to migraine centers after years of disabling disease, non-specific diagnoses and ineffective treatments. When patients are admitted to the center is therefore the time when their history in terms of disease evolution and healthcare costs is most effectively collected, but also when it is assumed that the treatment strategy offered to the patient will have a greater impact. For this reason, it was decided to conduct a large-scale retrospective and prospective observational study in order to draw a detailed picture of the situation of patients not followed by a specialized center and of the natural history of the disease once the pathway at the specialized center has started. Design A multicenter, observational, retrospective and prospective cohort study, aimed at obtaining a more detailed picture of the situation of patients not followed by a specialized center and of the natural history of the disease once the pathway at the specialized center has started.6,000 of the incident patients (defined as those who had their first visit during the 6 months preceding enrollment in the registry), will be invited to take part in a follow-up and expanded data collection study. Patients will be consecutively enrolled by specialists at each individual site.. Eligible patients who agree to take part in the study by signing an informed consent form will be assessed clinically and through a direct interview with a structured questionnaire organized in several ad hoc sections. Objectives: The aim of the study is: analyze episodic and chronic migraine in Italy from an epidemiological point of view, especially in terms of prevalence of the two forms of migraine and their endophenotypes in different population subgroups; 2. characterize the demographic distribution and clinical characteristics of patients (including the definition of endophenotypes); 3. measure the influence of the disease on the patient's daily activity, in terms of disability (assessed using the validated MIDAS and HIT-6 scales); 4. study the clinical and care pathway (patient journey) and identify the preferred care pathways based on the characteristics of the patients and the migraine subtype; 5. evaluate the prescribed pharmacological treatments, medical visits and diagnostic procedures performed (ascertaining the degree of adherence to current guidelines); 6. analyze the use of health resources by migraine patients, with particular attention to their impact on the SNS. Visits and Treatments: Baseline Visit: Patients enrolled in the study will undergo a thorough clinical and neurological examination. Follow-up Visits: Clinical data will continue to be collected over time, at each scheduled clinic visit based on the needs of clinical practice. Study Population: Adult patients of both sexes with episodic or chronic migraine who have recently attended a specialized migraine center in the I-GRAINE-NEW registry. Estimated Study Duration: The duration of each patient's participation in the study is 24 months from the date of the initial visit to the participating migraine site

The object of this study is to assess the effectiveness, safety, and tolerability of eptinezumab in a real life migraine population.

The effects of new technologies, particularly exergames, on the rehabilitation process of patients with hip arthroplasty have not yet been verified. For this reason, the aim of this study is to evaluate the effectiveness, in terms of balance recovery, of a balance rehabilitation program based on serious games in individuals with hip arthroplasty compared to conventional treatment.

Background and Rationale Cardiac rehabilitation (CR) is a key intervention for patients with chronic heart disease or recent acute cardiovascular events. In elderly and frail patients, CR aims not only to improve functional capacity but also to maintain or recover independence in daily activities. Hospitalization following an acute event often leads to bed rest, which-even after just 2-3 days-can cause hypokinetic syndrome, characterized by loss of muscle tone, orthostatic hypotension, decreased mobility, and psychological decline, including depression. Moreover, immobility increases thrombotic risk and vascular complications. To mitigate these effects, CR is initiated promptly after clinical stabilization and includes three phases: 1. Phase I - In-hospital rehabilitation 2. Phase II - Early outpatient rehabilitation 3. Phase III - Long-term maintenance Elderly patients are particularly vulnerable to falls due to the combined effects of reduced muscle strength, orthostatic hypotension, cognitive decline, and pre-existing sarcopenia-often exacerbated by acute events and immobility. Approximately 60% of cardiac patients hospitalized for acute events present with moderate-to-high fall risk. Fall risk in this population is multifactorial, involving cardiovascular issues (e.g., arrhythmias, orthostatic hypotension), medication effects, and non-cardiac factors such as vision loss, balance impairment, neuromuscular conditions, and cognitive deficits.

This study evaluates the effectiveness of upper limb rehabilitation using an end-effector robotic device with exercises designed to improve movements, strength, and coordination of the shoulder, elbow, and wrist in patients with Parkinson's disease who have mild to moderate disability, compared to conventional rehabilitation treatment. The study protocol will involve individuals diagnosed with PD according to the UK Parkinson's Disease Society Brain Bank criteria, who will be randomly assigned to one of the following groups: A - Experimental Group (EG) - robotic treatment for upper limb rehabilitation. B - Control Group (CG) - conventional treatment for upper limb rehabilitation. Secondary objectives include: \- Evaluating the effectiveness of an end-effector robotic system in terms of improving upper limb coordination and functionality through the ARAT test and the UPDRS. Identifying subgroups of participants who may benefit more from robotic therapy based on PD disease stage (Hoehn \& Yahr), age, and upper limb impairment. Analyzing the effects of robotic rehabilitation on quality of life. Assessing participants' compliance and satisfaction levels with the robotic system in terms of improving participation in upper limb rehabilitation.

The goal of this clinical trial is to study the clinical effects of a robotic rehabilitation treatment through a bilateral exoskeleton (Bilateral Robot-Assisted Therapy-BRAT) during standard rehabilitation, on motor recovery, compared to conventional arm re-education in people suffering from stroke in the subacute phase. The main question it aims to answer is what the effectiveness of Bilateral Robot-Assisted Therapy (BRAT) is in rehabilitating the upper limb in individuals with subacute stroke compared to conventional rehabilitation treatment in terms of motor function improvement as measured by the Fugl-Meyer Assessment - Upper Limb (FMA-UL), motor domain. Researchers will compare two groups (Experimental Group - EG and Control Group - CG) to see if the BRAT is more effective than conventional rehabilitation treatment in terms of motor recovery. Participants will be randomly assigned to one of the two treatment groups (EG or CG) and will be clinically and instrumentally evaluated at baseline (T0) and at the end of treatment (T1). EG, in addition to the standard rehabilitation treatment, will perform a 45-minute session of BRAT per day through the Arm Light Exoskeleton Hybrid (Alex RS - Wearable Robotics) robotic system. The CG, in addition to the standard routine rehabilitation treatment, will follow a conventional rehabilitation of the upper limbs without the use of technological devices. Finally, a telephone follow-up is scheduled three months after the end of the treatment.

Aim of the proposal is to create an interactive AI-based multicentre prospective database to provide information on how to improve the QoC for pts with HF.This will provide detailed information on pts characteristics,treatment practices, adherence to prescribed guideline-based optimal drug therapy,and outcomes.The database stems from a registry started two years ago,conceived to provide a contemporary snapshot on the adherence to the latest European GGLL for the therapeutic management of pts with HF.The database will be integrated with a specifically designed algorithm that provides an accurate feedback on whether patients are properly treated according to the ESC most recent recommendations.The expected outcomes are:-define non-adherence level to GGLL-based recommendations for treatment of HF;-provide information on initiation, adherence and persistence over time of the recommended treatment;-reduce medical inertia;produce practical implications to reduce morbidity and mortality

Although TeleRehabilitation (TR) is widely accepted as an appropriate model for the provision of professional health services in the field of physiotherapy, with already established standards, guidelines and policies, there are still few studies in the literature on the use of TR as a rehabilitation tool in people with Parkinson's Disease (PD). Therefore, further studies on the efficacy of TR in the management of motor and non-motor symptoms of PD are needed. The study TEMPO aims at assessing the efficacy (in terms of autonomy in carrying out the activities of daily life) of a home TR program based on serious games in people with PD compared to conventional day-hospital treatment.

This is a multicenter, observational, prospective, real-life study that will be conducted at Headache Centers, aimed at confirming the efficacy and safety of the combination of sumatriptan 85 mg with naproxen 500 mg. The combination of sumatriptan 85 mg and naproxen sodium 500 mg is indicated for the acute treatment of migraine attacks, with or without aura, in adult patients for whom sumatriptan monotherapy is insufficient. In two randomized studies, the sumatriptan/naproxen sodium combination demonstrated significantly greater efficacy (65% of participants-n=1461-reported pain freedom at 2 hours) compared to sumatriptan alone (55%), naproxen sodium alone (44%), or placebo (28%) when used as a late therapy for a single migraine episode in adults. Similar results were observed in a second study (n=1495), with 57% of participants achieving pain freedom within 2 hours after taking the sumatriptan/naproxen sodium combination, outperforming both sumatriptan monotherapy (50%) and naproxen sodium monotherapy (43%), as well as placebo (29%). This superiority was further assessed through sustained pain freedom over 24 hours, with an efficacy of 23-25% in participants treated with the sumatriptan/naproxen combination compared to placebo (7-8%; p\<0.001 for both studies) and its individual components (sumatriptan monotherapy: 14%-16%; p=0.009 and p\<0.001, naproxen sodium monotherapy: 10%). In four additional randomized studies, the combination was also found to be effective in menstrual migraine and dysmenorrhea, as well as in cases of poor response or intolerance to triptan therapy. In clinical trials, sumatriptan/naproxen sodium was generally well tolerated, with an overall safety profile similar to that of sumatriptan. The most common adverse events were consistent with those expected for sumatriptan and naproxen sodium.

The variable course of Alzheimer's disease (AD) and the paucity of adequate cures urges to implement new strategies for its early detection and clinical intervention. Studying the etiopathogenesis and pathophysiological mechanisms of AD is a necessary prerequisite for the development of new biomarkers and innovative therapies. Contrarily to anatomical structures, cortical connectivity networks are already deteriorated in early AD and could be a reliable marker of early cognitive decline. Our aim is to characterize the neurophysiological parameters in mild AD, in patients with mild cognitive impairment and in matched healthy subjects to identify discriminating criteria. Concurrently, the study of AD onset and progression in a mouse model, will allow evaluating the causal effect of inflammation on disease progression and to develop a new class of biomimetic anti-inflammatory nanoparticles formulated to have the intrinsic ability to induce brain's activated microglia to an M2 phenotype.

The present project aims to evaluate the facilitatory modulation of motor responses of the limb upper limb by tsDCS in patients with arm/hand hyposthenia after cerebral ischemia to verify the possible therapeutic benefits that this type of stimulation can induce in terms of of strength, dexterity and effectiveness in acts of daily living.

The goal of this observational study is to the purpose is to apply of ESPEN/EASO criteria for the diagnosis of sarcopenic obesity and calculation of OS prevalence in a sample of COPD patients. In addition, this study want to evaluate the impact of sarcopenic obesity on the respiratory function of COPD patients and the degree of severity of respiratory disease, assessed by spirometric examination; diaphragm thickness and excursion, by ultrasonographic study; performance, assessed by six-minute walk test (6-MWT); quality of life and degree of dyspnea (mMRC, Barthel dyspnea, S. George Respiratory Questionnaire); compliance and outcomes at the end of the respiratory rehabilitation course. Comparison with normal-weight patients with and without sarcopenia will help to better understand the clinical impact of sarcopenic obesity in this category of patients.

Our study purpose is to evaluate the predictive power of various clinical, neurophysiological, and neuroimaging biomarkers-acquired and analyzed using advanced and integrated techniques-on motor functional recovery and disability post-stroke. The goal is to construct an integrated individual biomarker algorithm with a high predictive value for outcomes.

The goal of this prospective observational study is to analyze the percentage of expression of B and NK cells expressing Mu opioid receptor on their surface, named Mu-Lympho-Marker (MLM), to measure pain progression in Osteoarthritis patients and its association with specific rehabilitation programs. In particular, we want to analyze the role of MLM as diagnostic biomarker of pain chronicization. The main aims are: * to explore the relationship between Mu+ B and NK cells percentage and pain progression in OA patients, also investigating whether this characteristic is associated to particular outcome of pharmacological and/or surgery interventions and rehabilitation * to characterize Mu+ B and NK cells in terms of maturation states, activation/inhibition and functional properties, as well as their ability to respond to Mu stimulation, in order to understand whether these cells can have a role in the pathogenesis of OA associated CP * to investigate the potential confounding effect of other biological and psychological elements in the relationship between the MLM and OA pain progression Researchers will compare two study groups: 1. Experimental group: subjects suffering from symptomatic knee OA. 1S)surgical subgroup: OA patients from the experimental group requiring primary TKA due to the failure of conservative treatment, thus undergoing surgical intervention; 2. Control group: subjects without any chronic pain, undergoing occupational health surveillance matched by age, sex and psychological profile with the experimental group patients Participants will be asked to do blood sample collections at specific time points to evaluate MLM stability over time and its modulation according to pharmacological/surgical and rehabilitation interventions. Subjects in the control group will undergo 2 blood sample collections. Pain assessment will be performed at all scheduled time points to correlate pain severity with Mu expression in B and NK cells.