[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658816":3},{"organization":4,"outcomesModule":7,"designInfo":58,"detailedDescription":65,"studyPopulation":61,"armGroups":66,"interventions":73,"overallOfficials":82,"centralContacts":94,"locations":105,"responsibleParty":124,"collaborators":61,"id":127,"slug":128,"hasResults":129,"nctId":130,"briefTitle":131,"officialTitle":132,"acronym":133,"eligibilityCriteria":134,"healthyVolunteers":129,"sex":135,"minAge":61,"maxAge":61,"enrollmentInfo":136,"targetDuration":61,"studyType":139,"phases":140,"briefSummary":141,"conditions":142,"keywords":145,"overallStatus":108,"whyStopped":61,"lastUpdateSubmitDate":156,"lastUpdatePostDateStruct":157,"startDateStruct":160,"completionDateStruct":162,"leadSponsor":164,"locationsCount":165},{"fullName":5,"class":6},"University of Siena","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":19,"otherOutcomes":36},[9,13,16],{"measure":10,"description":11,"timeFrame":12},"Change from baseline in plasma amyloid-beta concentrations","Change from baseline in plasma amyloid-beta 42 (Aβ42) and amyloid-beta 40 (Aβ40) concentrations following cervical lymphovenous anastomosis (LVA).","Baseline, 1 month, and 6 months after LVA",{"measure":14,"description":15,"timeFrame":12},"Change from baseline in plasma phosphorylated tau concentrations","Change from baseline in plasma phosphorylated tau 181 (p-tau181) and phosphorylated tau 217 (p-tau217) concentrations following cervical LVA.",{"measure":17,"description":18,"timeFrame":12},"Change from baseline in plasma NfL and GFAP concentrations","Change from baseline in plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) concentrations following cervical LVA.",[20,24,27,30,33],{"measure":21,"description":22,"timeFrame":23},"Change from baseline in Mini-Mental State Examination score","Change in Mini-Mental State Examination (MMSE) score from baseline. The MMSE ranges from 0 to 30, with higher scores indicating better cognitive function.","Baseline to 3, 6, and 12 months after LVA",{"measure":25,"description":26,"timeFrame":23},"Change from baseline in Montreal Cognitive Assessment score","Change in Montreal Cognitive Assessment (MoCA) score from baseline. The MoCA ranges from 0 to 30, with higher scores indicating better cognitive function.",{"measure":28,"description":29,"timeFrame":23},"Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale score","Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score from baseline. Scores range from 0 to 70, with higher scores indicating greater cognitive impairment.",{"measure":31,"description":32,"timeFrame":23},"Change from baseline in Neuropsychiatric Inventory score","Change in Neuropsychiatric Inventory (NPI) total score from baseline. Scores range from 0 to 144, with higher scores indicating greater neuropsychiatric symptom burden.",{"measure":34,"description":35,"timeFrame":23},"Change from baseline in Clinical Dementia Rating score","Change in Clinical Dementia Rating (CDR) global score from baseline. The CDR global score ranges from 0 to 3, with higher scores indicating greater dementia severity.",[37,41,44,47,50,54],{"measure":38,"description":39,"timeFrame":40},"Change from baseline in hippocampal volume on magnetic resonance imaging","Change from baseline in automated hippocampal volume measured on structural magnetic resonance imaging (MRI).","Baseline and 6 months after LVA",{"measure":42,"description":43,"timeFrame":40},"Change from baseline in cortical gray-matter volume on magnetic resonance imaging","Change from baseline in automated cortical gray-matter volume measured on structural magnetic resonance imaging (MRI).",{"measure":45,"description":46,"timeFrame":40},"Change from baseline in amyloid PET standardized uptake value ratio","Change from baseline in global and regional cerebral amyloid burden quantified using standardized uptake value ratio (SUVr) on amyloid positron emission tomography (PET).",{"measure":48,"description":49,"timeFrame":40},"Change from baseline in amyloid PET Centiloid value","Change from baseline in cerebral amyloid burden quantified using the Centiloid scale on amyloid positron emission tomography (PET).",{"measure":51,"description":52,"timeFrame":53},"Number of participants with procedure-related adverse events","Number of participants experiencing one or more adverse events considered related to cervical lymphovenous anastomosis, including infection, hematoma, wound-healing complications, transient swelling, neurological deficits, or anastomotic thrombosis or failure.","From LVA through 12 months after surgery",{"measure":55,"description":56,"timeFrame":57},"Number of participants with patent lymphovenous anastomosis","Number of participants with intraoperative evidence of lymphovenous anastomotic patency demonstrated by indocyanine-green fluorescence lymphography.","During the LVA procedure",{"allocation":59,"interventionModel":60,"interventionModelDescription":61,"primaryPurpose":62,"observationalModel":61,"timePerspective":61,"maskingInfo":63},"NA","SINGLE_GROUP",null,"TREATMENT",{"masking":64,"maskingDescription":61,"whoMasked":61},"NONE","Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) and pathological tau, accompanied by neuronal loss and progressive cognitive impairment. Recent evidence suggests that the glymphatic and meningeal lymphatic systems contribute to the clearance of brain waste products, including Aβ and tau, and that impaired drainage through the deep cervical lymphatic system may be involved in AD pathophysiology.\n\nEmerging preclinical and clinical evidence has suggested that restoration or enhancement of cervical lymphatic drainage may represent a potential therapeutic approach. Preliminary clinical studies have reported possible improvements in cognitive and clinical measures and favorable changes in AD-related biomarkers following cervical lymphatic surgery, although the available evidence remains limited and further prospective studies are needed.\n\nThe LymphDAD study is a prospective, single-center, pilot interventional study designed to explore the effects of restoring cervical lymphatic drainage in selected patients with AD who are not eligible for currently available disease-modifying therapies. Five participants will be enrolled.\n\nAll enrolled participants will undergo cervical lymphovenous anastomosis (LVA). LVA is a minimally invasive supermicrosurgical procedure in which patent lymphatic vessels are connected to small-caliber cervical veins to facilitate lymphatic drainage. The procedure will be performed under general anesthesia with indocyanine green fluorescence lymphography to identify lymphatic vessels and assess anastomotic flow. A small sample of lymphatic fluid will be collected intraoperatively from a lymphatic channel already exposed during the procedure for exploratory analysis of Aβ and tau.\n\nThe study will evaluate changes in circulating biomarkers, including Aβ42, Aβ40, phosphorylated tau (p-tau181 and p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Exploratory analyses of Aβ and tau in intraoperative lymphatic fluid will also be performed.\n\nNeuroimaging assessments will include structural magnetic resonance imaging (MRI) for brain volumetry and amyloid positron emission tomography (PET) for assessment of amyloid burden. Clinical and cognitive outcomes will be assessed using standardized instruments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Clinical Dementia Rating (CDR), and, when feasible, the EQ-5D quality-of-life questionnaire.\n\nAssessments will be performed at baseline and during follow-up. Blood biomarkers will be assessed at baseline, 1 month, and 6 months. Cognitive and clinical assessments will be performed at baseline, 3, 6, and 12 months. MRI volumetry and amyloid PET will be repeated at 6 months.\n\nThe primary purpose of this pilot study is exploratory. Outcomes will be evaluated as changes from baseline within each participant. The study does not include a control group and is not designed to establish the efficacy of LVA or demonstrate a definitive clinical benefit. The results will provide preliminary information regarding the feasibility and safety of the procedure and its possible effects on biological, imaging, cognitive, and clinical parameters, supporting the design of future controlled clinical studies.",[67],{"label":68,"type":69,"description":70,"interventionNames":71},"Cervical Lymphovenous Anastomosis (LVA)","EXPERIMENTAL","Participants in this single-arm pilot study will undergo cervical lymphovenous anastomosis (LVA), a minimally invasive supermicrosurgical procedure intended to enhance cervical lymphatic drainage. Patent cervical lymphatic vessels will be connected to small-caliber cervical venous branches under high magnification, with indocyanine green (ICG) fluorescence lymphography used to identify lymphatic vessels and assess anastomotic flow. A small sample of lymphatic fluid will be collected intraoperatively for exploratory analysis of amyloid-beta and tau biomarkers. Participants will continue standard-of-care treatment for Alzheimer's disease and other comorbidities throughout the study.",[72],"Procedure: Cervical lymphovenous anastomosis (LVA)",[74,79],{"type":75,"name":76,"description":77,"armGroupLabels":78,"otherNames":61},"PROCEDURE","Cervical lymphovenous anastomosis (LVA)","Microsurgical restoration of cervical lymphatic drainage by connecting patent lymphatic channels to small-caliber cervical venous branches. The procedure is performed along the posterior edge of the sternocleidomastoid muscle using supermicrosurgical techniques. Indocyanine green (ICG) fluorescence lymphography is used to identify lymphatic vessels and assess anastomotic flow. A small sample of lymphatic fluid is collected intraoperatively from a lymphatic channel already exposed during the procedure for exploratory analysis of amyloid-beta and tau biomarkers.",[68],{"type":75,"name":76,"description":80,"armGroupLabels":81,"otherNames":61},"Microsurgical restoration of cervical lymphatic drainage by connecting patent lymphatic channels to small-caliber cervical venous branches. In this study, lymphovenous anastomoses will be created along the posterior edge of the sternocleidomastoid muscle using supermicrosurgical techniques. Indocyanine green (ICG) fluorescence lymphography will guide lymphatic identification and assess anastomotic patency. A small sample of lymphatic fluid will also be collected intraoperatively from an exposed lymphatic channel for exploratory biomarker analysis.",[68],[83,87,91],{"name":84,"affiliation":85,"role":86},"Paolo Gennaro, Professor","University of Siena, Department of Biotechnology","STUDY_CHAIR",{"name":88,"affiliation":89,"role":90},"Domenico Plantone, Professor","University of Siena, Department of Neurology","PRINCIPAL_INVESTIGATOR",{"name":92,"affiliation":93,"role":90},"Federica Orsini, MD","University of Siena, Department of Nuclear Medicine",[95,101],{"name":96,"role":97,"phone":98,"phoneExt":99,"email":100},"Andrea Frosolini, MD","CONTACT","3939447318","0039","andreafrosolini@gmail.com",{"name":102,"role":97,"phone":103,"phoneExt":99,"email":104},"Carlo Manco, MD","3460221117","carlooo95.CM@gmail.com",[106],{"facility":107,"status":108,"city":109,"state":110,"zip":111,"country":112,"countryCode":113,"cosmosGeoPoint":114,"geoPoint":119,"contacts":120},"Azienda Ospedaliera Universitaria Le Scotte","RECRUITING","Siena","Tuscany","53100","Italy","IT",{"type":115,"coordinates":116},"Point",[117,118],11.33064,43.31822,{"lat":118,"lon":117},[121,122,123],{"name":96,"role":97,"phone":98,"phoneExt":99,"email":100},{"name":61,"role":97,"phone":61,"phoneExt":61,"email":100},{"name":96,"role":90,"phone":61,"phoneExt":61,"email":61},{"type":90,"investigatorFullName":125,"investigatorTitle":126,"investigatorAffiliation":5,"oldNameTitle":61,"oldOrganization":61},"Paolo Gennaro","Professor","100658816","restoring-cervical-lymphatic-drainage-in-alzheimers-disease-100658816",false,"NCT07854327","Restoring Cervical Lymphatic Drainage in Alzheimer's Disease","Evaluating the Effects of Restoring Lymphatic Drainage in Alzheimer's Disease: The LymphDAD Pilot Study","LymphDAD","Inclusion Criteria:\n\n* Diagnosis of Alzheimer's disease according to NIA-AA 2024 criteria.\n* Not eligible for other disease-modifying therapies.\n* Ability to personally provide written informed consent after clinical evaluation -of decisional capacity.\n\nExclusion Criteria:\n\n* Coagulopathy or active infection of the head and neck region.\n* Prior extensive cervical lymph node dissection or radiotherapy.\n* Uncontrolled systemic disease or contraindication to general anesthesia.\n* Participation in another interventional trial within the previous 3 months.\n* Known hypersensitivity or allergy to indocyanine green.\n* Evidence of alternative or concomitant causes of cognitive decline other than Alzheimer's disease, such as subdural hematoma, primary or metastatic brain malignancy, or normal-pressure hydrocephalus.\n* Current or recent treatment with immunosuppressive or immunomodulatory therapy within the previous 3 months.\n* Clinically significant infectious disease within the previous 6 months.\n* Severe psychiatric disorder that could interfere with cognitive assessment or study participation.\n* Pregnancy or breastfeeding.\n* End-stage malignant disease with an estimated life expectancy of less than 6 months.\n* History indicative of systemic autoimmune disease.\n* Inability to personally provide valid informed consent.","ALL",{"count":137,"type":138},5,"ESTIMATED","INTERVENTIONAL",[59],"Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with the accumulation of abnormal proteins, including amyloid-beta and tau, in the brain. Recent evidence suggests that the glymphatic and meningeal lymphatic systems, which contribute to the removal of waste products from the brain, may play a role in AD. In particular, impaired drainage through the deep cervical lymphatic system may contribute to the accumulation of disease-related proteins.\n\nThe LymphDAD study is a prospective, single-center pilot study designed to explore whether surgically improving cervical lymphatic drainage may be associated with changes in biological markers, brain imaging, and cognitive and clinical measures in selected patients with AD who are not eligible for currently available disease-modifying treatments.\n\nFive participants with AD will undergo a minimally invasive microsurgical procedure called lymphovenous anastomosis (LVA), in which small cervical lymphatic vessels are connected to nearby small veins to facilitate lymphatic drainage. During the procedure, a small sample of lymphatic fluid will also be collected for exploratory analysis of amyloid-beta and tau proteins.\n\nParticipants will undergo clinical and neuropsychological assessments, blood sampling, magnetic resonance imaging (MRI), and amyloid positron emission tomography (PET) before the procedure and during follow-up. Follow-up assessments will be performed at 1, 3, 6, and 12 months after surgery.\n\nThe study is exploratory and is not designed to demonstrate a definitive clinical benefit. Its primary purpose is to obtain preliminary information on the feasibility, safety, and possible biological and clinical effects of cervical LVA in AD, which may support the design of future controlled studies.",[143,144],"Alzheimer","Alzheimer Dementia (AD)",[146,147,148,149,150,151,152,153,154,155],"Alzheimer Disease","Alzheimer Dementia","Lymphovenous Anastomosis","Cervical Lymphatic Drainage","Deep Cervical Lymphatic System","Glymphatic System","Meningeal Lymphatics","Lymphovenous Bypass","Amyloid Beta","Tau","2026-09-26",{"date":158,"type":159},"2026-10-02","ACTUAL",{"date":161,"type":159},"2026-07-01",{"date":163,"type":138},"2028-12-31",{"name":5,"class":6},1]