Clinical trials

Disorders of consciousness (DOC), such as the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS), represent severe clinical conditions arising from acquired brain injury (ABI), exerting a profound impact on patients, caregivers, and healthcare systems. The clinical heterogeneity, diagnostic challenges, and paucity of robust evidence on the comparative efficacy of rehabilitation interventions underscore the need for a deeper understanding of the underlying neurophysiological, cognitive, and biological mechanisms involved in consciousness recovery. This monocentric ambispective observational study aims to investigate the effects of advanced neurorehabilitation treatments-including multimodal sensory stimulation, non-invasive neuromodulation via transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS), and the use of augmentative and alternative communication (AAC) devices with eye-tracking-on various facets of residual consciousness in patients diagnosed with DOC admitted to the Neurorehabilitation Unit of the IRCCS Centro Neurolesi "Bonino Pulejo" in Messina. The study design encompasses the collection of clinical and rehabilitation data from hospitalized patients undergoing treatment, both retrospectively and prospectively. Specifically, data from patients admitted and treated in the 36 months preceding study initiation, as well as those admitted and treated in the subsequent 36 months, will be included. Upon data collection, participants will be classified a posteriori as "responders" or "non-responders" based on whether they meet at least one of the following criteria: (I) an increase of ≥3 points on the Coma Recovery Scale-Revised (CRS-R) from baseline or a clinically relevant state transition (e.g., VS/UWS → MCS; MCS → emergence from MCS \[EMCS\]); (II) an increase of ≥10 points on the Functional Independence Measure (FIM) or ≥0.5 standard deviations (SD) from baseline; (III) an increase of ≥10 points on the Barthel Index or ≥0.5 SD from baseline. The primary objective is to estimate the proportion of responders and non-responders at the end of training or hospitalization. Secondary objectives include identifying variables predictive of treatment response at the end of intervention (training type/modality, aetiology, demographic factors, comorbidities), quantifying the dose-response gradient (number of sessions/session duration versus response probability), and assessing changes in neurophysiological, physiological, and biological parameters collected during hospitalization (neuroimaging examinations, neurofilament light chain \[NfL\] assays, EEG/event-related potentials \[ERP\], skin conductance response, heart rate frequency and variability, and oculomotor activity). Data will be analysed using descriptive statistics appropriate to variable distributions. The primary endpoint, defined as the proportion of responders at the end of training/hospitalization, will be evaluated using logistic regression models in an as-treated approach, reporting odds ratios and marginal estimates (risk ratios and absolute risk differences) with 95% confidence intervals (CI). Confounding will be addressed through multivariable adjustment and propensity score-based methods (inverse probability of treatment weighting \[IPTW\]/overlap weighting). Continuous secondary outcomes will be analysed with linear models or linear mixed-effects models for repeated measures. Dose-response relationships will be explored, alongside sensitivity and subgroup analyses. All analyses will be performed using R software (version 4.4.2), employing two-sided tests with a significance level of α=0.05. The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines.

The goal of this clinical trial is to evaluate the effectiveness of a telerehabilitation program combined with a virtual reality (VR) app in improving cognitive performance and social skills in patients with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). The main questions it aims to answer are: Can a VR telerehabilitation program improve cognitive functions and social skills in patients with SCD and MCI? Are there measurable changes in brain activity, eye movements, and gait patterns after the intervention? Researchers will compare telerehabilitation with a VR group (Experimental Group - EG) to a traditional paper-based cognitive rehabilitation group (Active Control Group - aCG) to determine which approach is more effective. Participants will: Undergo an initial assessment, including neurological exams, neuropsychological tests, brain MRI, EEG, eye movement analysis, and gait evaluation. Participate in a 6-week intervention program: EG: Use VR apps on smartphones/tablets at home, guided remotely by a therapist. aCG: Perform traditional cognitive exercises using paper-based tasks. Complete follow-up assessments immediately after the intervention and again after three months. This study will help determine whether telerehabilitation with VR can provide measurable cognitive and social benefits, contributing to improved care strategies for individuals at risk of dementia.

Based on study literature, the investigators can say that our study aims to give an explanation not only from a behavioral point of view but also with respect to what are the neuronal mechanisms underlying our ability to perceive and analyze our own and others' actions. This is essential to fully understand the complexity of our social behaviors. The knowledge of these mechanisms has a high value and relevant implications for many research fields both within and outside the neurosciences. The project aims to study the neurobehavioral correlates of verbal and non-verbal communication. Through the use of non-invasive behavioral and neurophysiological techniques, the study intends to highlight the neurobehavioral markers that allow to quantify the temporal evolution of communication dynamics in healthy subjects.

The GM-REHAB-2025 study aims to evaluate the impact of physiotherapy interventions using the C-Mill treadmill, with and without semi-immersive virtual reality, on gut microbiota and metabolic parameters in patients with Parkinson's disease. Three groups will be involved: one undergoing conventional physiotherapy, one treated with the C-Mill without virtual reality (VR), and one treated with C-Mill technology combined with VR. Clinical assessments and the collection of biological samples (stool, serum, and plasma) will be carried out at three time points: at baseline, at the end of treatment (21 days), and after 3 months.

Evidence indicates that many mental disorders in adulthood originate during adolescence, with a typical onset between the ages of 14 and 18, especially for anxiety, mood, and behavioral disorders. Over the past 20 years, the prevalence of psychiatric disorders among children and adolescents has increased globally, influenced by factors such as environmental stress, digital technologies, socioeconomic inequalities, and the consequences of the COVID-19 pandemic. Approximately one in seven adolescents worldwide suffers from a diagnosable mental disorder, with a growing trend, especially in high-income countries. A multidimensional and multi-informant assessment, integrating the perspectives of adolescents and parents, is essential for the early detection of signs of psychological distress and the definition of targeted interventions. Main objective: To assess the mental health of adolescents (aged 11-18) using multidimensional psychometric tools to identify early signs of distress and vulnerability.

Executive functions and metaphonological skills are closely interconnected in supporting language development and learning processes.Investigating this relationship could offer new insights into how executive and metaphonological skills interact, supporting the development of integrated intervention strategies targeting both cognitive and linguistic domains. This study aims to evaluate the effectiveness of a rehabilitation intervention using a virtual reality system (VRRS) in enhancing executive functions and monitoring metaphonological skills in children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD).The aim is to explore whether a semi-immersive digital cognitive training protocol can lead to measurable improvements in executive functions, and whether such improvements are associated with gains in metaphonological skills. Participants will present deficits in executive functions and metaphonological skills and will undergo pre- and post-intervention assessments. These assessments include standardized neuropsychological and speech-language pathology tools designed to detect impairments in attention, inhibition, working memory, phonological awareness, and behavior in home and school settings.

Neurodevelopmental disorders, such as Cerebral Palsy (CP), Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), are complex conditions that affect various aspects of children's development. Despite advancements in treatments, conventional rehabilitative interventions tend to focus on specific aspects, often overlooking the holistic needs of the patient. Many of these interventions fail to engage children, who may feel uninvolved or demotivated. Innovative technologies, such as immersive virtual reality (IVR), offer a promising alternative to make rehabilitation more engaging and comprehensive. This study aims to evaluate the effects of IVR-based rehabilitation on children and adolescents with neurodevelopmental disorders, focusing on improvements in cognitive, motor, and social functions. We hypothesize that IVR will enhance social interaction, attention, motor skills, and overall quality of life. The study will include children and adolescents aged 8 to 18 years, diagnosed with ADHD, ASD, and cerebral palsy. The CAR-EN platform, which provides a highly customizable therapeutic environment, will be used. Assessments will measure cognitive, motor, and social skills before and after the intervention. We expect immersive virtual reality to lead to significant improvements in the participants' cognitive, motor, and social abilities. These findings could potentially contribute to a shift in therapeutic guidelines, offering more effective treatments for children with neurodevelopmental disorders.

The goal of this clinical trial is to learn if sensor-based robotic upper limb rehabilitation can improve cognitive and motor functions in adults with neurological and neurodegenerative disorders, including Parkinson's disease, multiple sclerosis, and stroke. The main questions it aims to answer are: Does sensor-based robotic rehabilitation improve cognitive functions such as attention, memory, and executive functions? Does this rehabilitation lead to better motor recovery and daily functioning compared to conventional therapy? Researchers will compare the experimental group receiving robotic rehabilitation with cognitive tasks to the control group receiving conventional therapy to see if the robotic approach leads to greater improvements in both cognitive and motor outcomes. Participants will: Receive upper limb rehabilitation using robotic devices and virtual reality-based exercises or conventional therapy Complete a series of neuropsychological assessments before and after the intervention to measure cognitive changes Complete motor function tests before and after the intervention to evaluate physical improvements Participate in 25 training sessions, 2-3 times per week, each lasting 60 minutes

Mild Cognitive Impairment (MCI) is a condition characterized by cognitive deterioration greater than what is expected from normal aging, representing an important risk factor for the development of dementia. Early assessment of cognitive functions is therefore essential for promptly identifying any signs of decline. In addition to cognitive aspects, it is equally important to consider the possible psychopathological profile of patients, as such disorders can significantly influence the progression of the disease, quality of life, and the ability to manage daily activities. This protocol aims to explore the presence of psychopathological disorders in patients with MCI, with particular attention to their impact on awareness of cognitive deficits (anosognosia) and on the subjective perception of difficulties in daily life, especially in social and work contexts. The study seeks to outline a comprehensive picture of the psychopathological profile in patients with MCI, facilitating the identification of targeted and personalized interventions capable of improving clinical management and the overall well-being of the individual.

Glucosinolates (GLs) are phytocompounds mainly found in the Cruciferae (Brassicacea) and Moringa oleifera plants. The hydrolysis of GLs by myrosinase led to the production of isothiocyanate (ITCs). ITCs consumption was associated with different health promoting effects, including to neuroprotective, anti-oxidant and anti-inflammatory capacities. In particular, they showed neuroprotective effects in experimental models of neurodegenerative diseases, including multiple sclerosis (MS) and Parkinson's disease (PD). From different GLs, different ITCs are originated. In particular, from glucoraphanin (GRA) the ITC sulforaphane (SFN) is obtained. The PI of the project is one of the proprietor of a patent (EP2908850B1) for the application of (Rs)-GRA with myrosinase in a buffered solution for the treatment of neurodegenerative diseases. The aim of this project is to evaluate the effects of the administration of bioactivated GRA in different cohorts of adult patients, affected by MS and PD, but also a cohort of pediatric patients affected by neuromuscolar and degenerative diseases. The effects of bioactivated (Rs)-GRA administration will be evaluated with a combination of clinical evaluations and a multiomic (metabolomic, genomic) approach.

Headache, in its episodic and chronic forms, cannot be considered solely as an isolated neurological symptom, but as a complex condition of a bio-psycho-social nature. While in the episodic form the painful episodes occur intermittently and have a variable impact on daily life, in the chronic form the disease evolves towards persistent pain, with more significant consequences on personal, social and work functioning. The following study protocol aims to investigate in an integrated manner the neurological, cognitive and psychological mechanisms involved in headache, with particular attention to the differences between episodic and chronic forms. The main objective is to assess the neuropsychological profiles and pain response of patients, monitoring their evolution over a period of approximately six months, considering the impact of central sensitisation, personality structure and any psychopathological comorbidities on pain management and treatment adherence. The protocol adopts a multidimensional approach aimed at optimising therapeutic efficacy and improving patients' quality of life, preventing progression to chronicity.

Dementia, in its various forms, is characterized by a generalized cognitive decline that can significantly compromise personal autonomy and quality of life. Mild Cognitive Impairment (MCI), although not classified as an overt form of dementia, represents a condition at evolutionary risk and is considered a crucial transitional stage for the early detection of cognitive decline. Understanding the impact of dementia and MCI from a multidimensional perspective is now essential to fully grasp the repercussions of these conditions on patients' daily lives. The present protocol aims to investigate key aspects related to these disorders, with the objective of exploring cognitive functioning, the degree of impairment in activities of daily living, and the presence of neuropsychiatric symptoms. Through an integrated and multidisciplinary approach, the study seeks to enhance clinical management and patient care, promoting more effective, targeted, and personalized interventions.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, painless brain stimulation treatment that uses low-intensity direct electrical currents to stimulate specific parts of the brain. Transcranial Direct Current Stimulation (tDCS) can both facilitate anodic stimulation and inhibit cathodic stimulation specific brain areas since many neurological and psychiatric disorders are connected to hypoactivity or hyperactivity in specific areas of the nervous system. This phenomenon is based on two processes: the reorganization of functional neural circuits and their reconstruction. In light of the studies mentioned above, it is presumed that Transcranial Direct Current Stimulation (tDCS) can be a valuable tool to facilitate the process of neuroplasticity in individuals with chronic neurological diseases and in patients with impaired consciousness following severe brain injury. A previous study demonstrated that a single session of transcranial direct current electrical stimulation could temporarily improve signs of consciousness in patients in a minimally conscious state (MCS)

\*\*Brief Summary\*\* The study aims to explore how the integration of visual and motor systems can be trained and enhanced to improve gait rehabilitation in patients with various neurological and cardiovascular conditions. Scientific evidence highlights that physical activity requires coordination and precise processing of visual, auditory, and sensory information from the external environment, which is then integrated at the brain level. This process establishes synaptic connections that direct the movement of arms, hands, legs, and the trunk through bottom-up and top-down mechanisms. However, inaccurate or incomplete perceptual information can impair performance, even when accurate visual stimuli are provided, emphasizing the importance of assessing and enhancing visuo-motor integration. The research investigates the central mechanisms controlling peripheral muscle activation patterns during gait. While over-ground walking in healthy individuals generally does not activate the prefrontal cortex except in dual-task scenarios, evidence suggests that post-stroke patients exhibit increased prefrontal cortex metabolism during walking. Recent studies have shown that gait training with exoskeletal systems improves walking patterns in post-stroke patients by altering muscle activation patterns and increasing fronto-parietal connectivity. This study seeks to answer the following question: How do central and peripheral mechanisms interact to influence gait rehabilitation outcomes, and what role do visuo-motor integration and neuroplasticity play in this process? To address this, advanced neuroimaging technologies such as fMRI, dtMRI, and NIRS will be employed to investigate these mechanisms in vivo.

The aim of this project is to develop an Augmentative and Alternative Communication intervention through the use of Eye tracker system.