[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100618869":3},{"organization":4,"outcomesModule":7,"designInfo":62,"detailedDescription":72,"studyPopulation":65,"armGroups":73,"interventions":96,"overallOfficials":132,"centralContacts":137,"locations":65,"responsibleParty":146,"collaborators":65,"id":149,"slug":65,"hasResults":150,"nctId":151,"briefTitle":152,"officialTitle":153,"acronym":154,"eligibilityCriteria":155,"healthyVolunteers":150,"sex":156,"minAge":157,"maxAge":158,"enrollmentInfo":159,"targetDuration":65,"studyType":162,"phases":163,"briefSummary":165,"conditions":166,"keywords":168,"overallStatus":175,"whyStopped":65,"lastUpdateSubmitDate":176,"lastUpdatePostDateStruct":177,"startDateStruct":180,"completionDateStruct":182,"leadSponsor":184,"locationsCount":65},{"fullName":5,"class":6},"Fondazione Policlinico Universitario Campus Bio-Medico","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":50},[9],{"measure":10,"description":11,"timeFrame":12},"Evaluation of objective changes in gait speed (m\u002Fs) through gait analysis.","Gait speed (m\u002Fs) is measured using a 3D optoelectronic motion-capture system with inertial sensors during level walking on a 10-meter walkway with integrated force platforms. Standard lower-limb reflective markers and surface EMG are used to capture kinematic and muscle-activation patterns. Average gait speed is calculated as the mean forward velocity.","Baseline (T0) and Post-intervention (T1, 4 weeks)",[14,18,22,26,29,33,36,38,41,44,47],{"measure":15,"description":16,"timeFrame":17},"Spatiotemporal and Kinematic Gait Parameters assessment (gait quality parameter).","Spatiotemporal and kinematic gait parameters are measured using a 3D motion-capture system with inertial sensors and surface EMG while participants walk across a walkway with integrated force platforms. Parameters include stance and swing phase duration (s), single and double support time (s), step and stride length (cm) and variability (%), swing speed (m\u002Fs) and cadence (steps\u002Fmin), lower-limb joint flexion-extension angles (°), peak vertical ground reaction force (N\u002Fkg), and muscle-activation timing (ms) from surface EMG. All listed parameters will be analyzed collectively as a single composite secondary outcome and will not be reported as separate outcome measures.","Baseline (T0), Post-intervention at 4 weeks (T1)",{"measure":19,"description":20,"timeFrame":21},"Change in Motor Function (MDS-UPDRS Part III Total Score).","Motor function will be assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), which evaluates bradykinesia, rigidity, tremor, posture, and gait-related motor signs. Total scores range from 0 to 132, with higher scores indicating worse motor impairment. Improvement is reflected by a decrease in the MDS-UPDRS III score.","Baseline (T0) and Post-intervention at 4 weeks (T1).",{"measure":23,"description":24,"timeFrame":25},"Cognitive Function (RBANS Total Score) assessment.","Cognition is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which evaluates immediate memory, visuospatial\u002Fconstructional abilities, language, attention, and delayed memory. Total scores range from 40 (severely impaired) to 160 (very superior), with higher scores indicating better performance.","Baseline (T0) and Post-intervention at 4 weeks (T1)",{"measure":27,"description":28,"timeFrame":25},"Quality of Life (PDQ-39 Total and Domain Scores) assessment.","Quality of life is assessed using the Parkinson's Disease Questionnaire-39 (PDQ-39), which measures mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Domain and total scores range from 0 to 100, with higher scores indicating poorer quality of life. Improvement is reflected by a decrease in PDQ-39 scores.",{"measure":30,"description":31,"timeFrame":32},"Change in Gait Speed from Post-intervention to Follow-up.","Average gait speed (m\u002Fs) is measured using a 3D motion-capture system during level walking. This outcome represents the change in gait speed between the post-intervention visit (T1) and the follow-up visit (T2) to evaluate persistence of treatment effects.","Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)",{"measure":34,"description":35,"timeFrame":32},"Change in Spatiotemporal and Kinematic Gait Parameters (gait quality parameter) from Post-intervention to Follow-up.","Spatiotemporal and kinematic gait parameters (stance and swing duration (s), single and double support time (s), step and stride length (cm) and variability (%), swing speed (cm\u002Fs) and cadence (steps\u002Fmin), joint flexion-extension angles (°), peak vertical ground reaction force (N\u002Fkg), and muscle-activation timing (ms)) are assessed with 3D motion capture, force platforms, and surface EMG. All listed parameters will be analyzed collectively as a single composite secondary outcome and will not be reported as separate outcome measures. This outcome reflects change in these parameters from T1 to T2.",{"measure":37,"description":20,"timeFrame":32},"Change in Motor Function (MDS-UPDRS Part III Total Score) from Post-intervention to Follow-up.",{"measure":39,"description":40,"timeFrame":32},"Change in Cognitive Function (RBANS Total Score) from Post-intervention to Follow-up.","Cognition is assessed with the RBANS, which evaluates immediate memory, visuospatial\u002Fconstructional abilities, language, attention, and delayed memory. This outcome captures the change in RBANS total score from T1 to T2 to evaluate persistence of cognitive effects. Higher scores indicate better performance.",{"measure":42,"description":43,"timeFrame":32},"Change in Quality of Life (PDQ-39) from Post-intervention to Follow-up.","Quality of life is assessed using the PDQ-39, which measures mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. This outcome represents the change in PDQ-39 total score from T1 to T2, where higher scores indicate poorer quality of life and improvement is reflected by a decrease in scores.",{"measure":45,"description":46,"timeFrame":32},"Change in Inflammatory Biomarkers (Serum and Salivary Cytokines) from Post-intervention to Follow-up.","Serum and salivary levels of inflammatory cytokines (TNF-α, IL-1β, IL-13, IL-10, IL-6) will be measured using standardized ELISA or multiplex immunoassays. Concentrations will be expressed in pg\u002FmL. Cytokines will be analyzed collectively as a composite inflammatory outcome.",{"measure":48,"description":49,"timeFrame":32},"Change in Neurodegenerative Biomarker Levels (α-Synuclein) from Post-intervention to Follow-up.","Serum and salivary levels of α-synuclein will be measured using standardized immunoassays. Concentrations will be expressed in ng\u002FmL.",[51,55,58,60],{"measure":52,"description":53,"timeFrame":54},"Imaging Outcomes (PCASL).","Brain perfusion will be assessed using pseudo-continuous arterial spin labeling (PCASL). Imaging is performed at baseline (T0) and post-treatment (T1). Primary imaging endpoints include:\n\n\\- Change in cerebral blood flow (CBF) in locomotor and motor-control regions (PCASL)","Baseline (T0) and Post-treatment at 4 weeks (T1)",{"measure":56,"description":57,"timeFrame":54},"Imaging Outcomes (fMRI).","Functional connectivity will be assessed by functional MRI (fMRI). Imaging is performed at baseline (T0) and post-treatment (T1). The fMRI assessment includes a simulated gait task using a custom pedal system with synchronized visual feedback.\n\nPrimary imaging endpoints include:\n\n\\- Change in functional connectivity within gait-related cortical-subcortical networks (fMRI).",{"measure":59,"description":46,"timeFrame":54},"Inflammatory Biomarkers (Serum and Salivary Cytokines)",{"measure":61,"description":49,"timeFrame":54},"Neurodegenerative Biomarker (α-Synuclein)",{"allocation":63,"interventionModel":64,"interventionModelDescription":65,"primaryPurpose":66,"observationalModel":65,"timePerspective":65,"maskingInfo":67},"RANDOMIZED","PARALLEL",null,"TREATMENT",{"masking":68,"maskingDescription":65,"whoMasked":69},"DOUBLE",[70,71],"PARTICIPANT","OUTCOMES_ASSESSOR","Parkinson's disease (PD) is characterized by gait disturbance, impaired mobility, and progressive involvement of neural circuits responsible for locomotion and postural control. Although physical therapy is effective, its benefits are often modest and short-lived. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that activates the auricular branch of the vagus nerve and engages ascending brainstem pathways involved in motor control, arousal regulation, and inflammatory modulation. Previous studies have shown that taVNS can influence subcortical β-band oscillations, improve gait parameters, enhance cognitive performance, and modulate systemic inflammatory markers in individuals with PD.\n\nThis randomized, double-blind, sham-controlled clinical trial evaluates whether pairing taVNS with gait-focused rehabilitation enhances motor outcomes and neural plasticity in individuals with de novo PD. Participants are newly diagnosed (≤6 months) and undergo a 4-week rehabilitation program consisting of conventional physiotherapy, with or without sensorized treadmill training. Active or sham taVNS is administered during each therapy session. The study includes four parallel arms to independently assess the contributions of taVNS and treadmill-based gait training.\n\nOutcomes are assessed at baseline (T0), immediately post-intervention (T1), and at a 4-week follow-up visit (T2). Primary and secondary outcomes include quantitative gait parameters, clinical motor scales, cognitive performance, and quality-of-life measures. Exploratory outcomes include changes in cerebral blood flow measured with pseudo-continuous arterial spin labeling (PCASL), functional connectivity during a simulated gait task using fMRI, and blood and salivary biomarkers of inflammation and neurodegeneration (e.g., TNF-α, interleukins, and α-synuclein).\n\nThe study aims to determine whether taVNS enhances rehabilitation-induced improvements in gait, whether these benefits persist beyond the treatment period, and whether taVNS induces measurable changes in brain perfusion, functional networks, or circulating biological markers relevant to PD pathophysiology. Results may support the development of a scalable, non-invasive therapeutic approach that can be integrated into early PD management.",[74,82,86,92],{"label":75,"type":76,"description":77,"interventionNames":78},"taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)","ACTIVE_COMPARATOR","Participants will receive active taVNS, stimulation parameters: 25 Hz frequency, 200 μs pulse width, and intensity adjusted to the individual's sensory threshold, delivered to the left auricular tragus for the duration of each session (\\~30 minutes). During stimulation, participants will perform treadmill walking on a sensorized treadmill system with simultaneous conventional physical therapy exercises focused on posture, balance, and gait re-education. Sessions will occur three times per week for four weeks (12 sessions total).",[79,80,81],"Procedure: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)","Other: Conventional Physical Therapy (cPT)","Other: Sensorized Treadmill Training (STT)",{"label":83,"type":76,"description":84,"interventionNames":85},"taVNS paired with conventional physical therapy (cPT)","Participants will receive active taVNS (same parameters and device as Arm 1) during conventional physical therapy sessions without treadmill training.\n\nSessions will occur three times per week for four weeks.",[79,80],{"label":87,"type":88,"description":89,"interventionNames":90},"Sham taVNS paired with STT and cPT","SHAM_COMPARATOR","Sham stimulation will consist of few impulses delivered at 25 Hz for a duration of 60'' before waning, creating the same initial sensation without continuous current delivering.\n\nParticipants will simultaneously undergo treadmill-based and conventional physical therapy as described above.\n\nSchedule: three sessions per week for four weeks.",[91,80,81],"Procedure: Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS)",{"label":93,"type":88,"description":94,"interventionNames":95},"Sham taVNS paired with cPT","Participants will receive sham stimulation (same device and sham procedure as Arm 3) during conventional physical therapy sessions without treadmill training.\n\nSchedule: three sessions per week for four weeks.",[91,80],[97,108,116,123],{"type":98,"name":99,"description":100,"armGroupLabels":101,"otherNames":102},"PROCEDURE","Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)","Active taVNS delivered at the inner tragus of the left ear (25 Hz, 200 μs, intensity at sensory threshold)",[83,75],[103,104,105,106,107],"Transcutaneous Auricular Vagus Nerve Stimulation","taVNS","nVNS","tVNS","Transauricular Vagus Nerve Stimulation",{"type":98,"name":109,"description":110,"armGroupLabels":111,"otherNames":112},"Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS)","Sham taVNS using the electrode placement as active taVNS but without electrical stimulation beyond the initial sensation.",[87,93],[113,114,115],"Sham transcutaneous auricular vagus nerve stimulation","sham taVNS","sham",{"type":6,"name":117,"description":118,"armGroupLabels":119,"otherNames":120},"Conventional Physical Therapy (cPT)","Conventional Physical Therapy delivered to all groups consist of exercises aimed at posture alignment, reduction of hypertone, balance improvement and overground gait training.",[87,93,83,75],[121,122],"Conventional Physical Therapy","cPT",{"type":6,"name":124,"description":125,"armGroupLabels":126,"otherNames":127},"Sensorized Treadmill Training (STT)","Sensorized Treadmill Training consist of a sensorized gait treadmill training with continuous visual feedback combined with dual cognitive tasks (e.g. repeat digits, repeat sequence of words, counting down the dates).",[87,75],[128,129,130,131],"Sensorized Treadmill Training","STT","treadmill","sensorized treadmill",[133],{"name":134,"affiliation":135,"role":136},"Massimo Marano, MD, PhD","Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy","PRINCIPAL_INVESTIGATOR",[138,142],{"name":134,"role":139,"phone":140,"phoneExt":65,"email":141},"CONTACT","+39 3333488802","m.marano@policlinicocampus.it",{"name":143,"role":139,"phone":144,"phoneExt":65,"email":145},"Gaia Anzini, MD","+39 3662007406","gaia.anzini@unicampus.it",{"type":136,"investigatorFullName":147,"investigatorTitle":148,"investigatorAffiliation":5,"oldNameTitle":65,"oldOrganization":65},"Massimo Marano","Principal Investigator","100618869",false,"NCT07337226","Association of VAgus Nerve Stimulation and Treadmill Training for GAit Rehabilitation in DE Novo Parkinson's Disease","Association of VAgus Nerve Stimulation and Treadmill Training for GAit Rehabilitation in DE Novo Parkinson's Disease (AVANTGARDE-PD)","AVANTGARDE-PD","Inclusion Criteria:\n\n* Idiopathic PD diagnosis within 6 months, confirmed by neurologist specialized in Parkinson's disease and movement disorders;\n* Ability to walking independently for at least 10 meters unassisted;\n* Age included between 50 and 80;\n* MMSE \\> 24;\n* On stable therapy for at least 1 month prior to the experiment.\n\nExclusion Criteria:\n\n* Clinical and radiological red flags for atypical, vascular parkinsonism or alternative diagnosis (e.g., normal pressure hydrocephalus);\n* Levodopa equivalent daily dose \\> 300 mg;\n* Any contraindication for taVNS (e.g., ear lesions, auditory prosthesis)\n* Any contraindication for MRI (e.g., non compatible pacemakers or prosthesis, claustrophobic subjects);\n* Concomitant neurological, orthopedic or active medical\u002Foncological condition that would affect participating to the study;\n* Attempting to other neurorehabilitation programs within 3 months.","ALL","50 Years","80 Years",{"count":160,"type":161},60,"ESTIMATED","INTERVENTIONAL",[164],"NA","The goal of this clinical trial is to learn if transcutaneous auricular vagus nerve stimulation (taVNS) can improve gait and brain function in people with diagnosis of idiopathic Parkinson's disease (PD) within 6 months. It will also help researchers learn about the safety and biological effects of taVNS when used together with physical therapy.\n\nThe main questions it aims to answer are:\n\n* Does taVNS paired with physical therapy improve walking speed and gait performance in people with PD?\n* Does taVNS change brain activity or breain perfusion related to movement?\n* Does taVNS reduce markers of inflammation and neurodegeneration in blood and saliva? Researchers will compare active taVNS to sham (placebo) stimulation to see if active taVNS works better when paired with physical therapy.\n\nParticipants will:\n\n* Attend 12 rehabilitation sessions over 4 weeks (three per week)\n* Receive either active or sham taVNS during each session while doing treadmill and conventional physical therapy\n* Undergo gait and cognitive testing, MRI scans, and blood and saliva collection before and after treatment\n* Return for a follow-up visit four weeks after therapy to check how long the effects last",[167],"Idiopathic Parkinson's Disease (PD)",[169,170,171,172,173,174],"Parkinson's disease","Vagus nerve stimulation","non invasive brain stimulation","treadmill training","freezing of gait","rehabilitation","NOT_YET_RECRUITING","2026-01-04",{"date":178,"type":179},"2026-01-13","ACTUAL",{"date":181,"type":161},"2026-01",{"date":183,"type":161},"2027-10",{"name":5,"class":6}]