AlzheimerLymphDADNCT07854327
Restoring Cervical Lymphatic Drainage in Alzheimer's Disease
A study testing Cervical lymphovenous anastomosis (LVA) in people with Alzheimer and Alzheimer Dementia (AD), run by University of Siena at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alzheimer, Alzheimer Dementia (AD)
- What is being tested?
- Cervical lymphovenous anastomosis (LVA)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jul 2026to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of Alzheimer's disease according to NIA-AA 2024 criteria.
- Not eligible for other disease-modifying therapies.
- Ability to personally provide written informed consent after clinical evaluation -of decisional capacity.
Who cannot join
- Coagulopathy or active infection of the head and neck region.
- Prior extensive cervical lymph node dissection or radiotherapy.
- Uncontrolled systemic disease or contraindication to general anesthesia.
- Participation in another interventional trial within the previous 3 months.
- Known hypersensitivity or allergy to indocyanine green.
- 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.
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- Current or recent treatment with immunosuppressive or immunomodulatory therapy within the previous 3 months.
- Clinically significant infectious disease within the previous 6 months.
- Severe psychiatric disorder that could interfere with cognitive assessment or study participation.
- Pregnancy or breastfeeding.
- End-stage malignant disease with an estimated life expectancy of less than 6 months.
- History indicative of systemic autoimmune disease.
- Inability to personally provide valid informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliera Universitaria Le Scotte
Siena, Tuscany, 53100
Andrea Frosolini, MD, 3939447318 ext. 0039, andreafrosolini@gmail.com
andreafrosolini@gmail.com
About this study
Official title: Evaluating the Effects of Restoring Lymphatic Drainage in Alzheimer's Disease: The LymphDAD Pilot Study
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.
The 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.
Read more
Five 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.
Participants 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.
The 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.
Read the detailed description
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.
Emerging 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.
The 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.
All 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.
The 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.
Neuroimaging 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.
Assessments 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.
The 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.
- Conditions
- Alzheimer, Alzheimer Dementia (AD)
- Being tested
- Cervical lymphovenous anastomosis (LVA)
- Keywords
- Alzheimer Disease, Alzheimer Dementia, Lymphovenous Anastomosis, Cervical Lymphatic Drainage, Deep Cervical Lymphatic System, Glymphatic System, Meningeal Lymphatics, Lymphovenous Bypass, Amyloid Beta, Tau
- Medical subject headings
- Alzheimer Disease, Plaque, Amyloid, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cervical lymphovenous anastomosis (LVA)Procedure or surgery
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.
Cervical lymphovenous anastomosis (LVA)Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Cervical lymphovenous anastomosis (LVA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline, 1 month, and 6 months after LVA
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.
Measured: Baseline, 1 month, and 6 months after LVA
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.
Measured: Baseline, 1 month, and 6 months after LVA
Secondary outcomes (5)
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.
Measured: Baseline to 3, 6, and 12 months after LVA
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.
Measured: Baseline to 3, 6, and 12 months after LVA
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.
Measured: Baseline to 3, 6, and 12 months after LVA
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.
Measured: Baseline to 3, 6, and 12 months after LVA
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.
Measured: Baseline to 3, 6, and 12 months after LVA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study start1 Jul 2026
- Primary completion1 Jul 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AlzheimerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Siena
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paolo Gennaro, University of Siena
- Investigators
- Paolo Gennaro, Professor, Study chair, University of Siena, Department of BiotechnologyDomenico Plantone, Professor, Principal investigator, University of Siena, Department of NeurologyFederica Orsini, MD, Principal investigator, University of Siena, Department of Nuclear Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07854327
- Sponsor's protocol ID
- LymphDAD
- Acronym
- LymphDAD
- Status last verified
- Sep 2026
- First submitted
- 19 Aug 2026
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Imholz C, Schaller C, Watson JA, Zurfluh CE, Grigorean A, Lindenblatt N. Robotic-assisted lymphovenous anastomosis to treat periorbital lymphedema and systematic review of lymphatic reconstruction of face and neck lymphedema. J Robot Surg. 2025 Jul 12;19(1):380. doi: 10.1007/s11701-025-02552-6. Xie Q, Pak CJ, Kwon J, Chao SC, Hong JP . Potential Role of Lymphovenous Bypass in Mitigating Alzheimer's Disease Dementia. Arch Plast Surg. 2025 Jul 23;52(4):247-252. doi: 10.1055/a-2627-9243. Chen JY, Zhao DW, Yin Y, Gui L, Chen X, Wang XM, Wang PB, Zuo CH, Lai ZP , Li C, Wang R, Xian JS, Chen Z, Feng H, Hu R. Deep cervical lymphovenous anastomosis (LVA) for Alzheimer's disease: microsurgical procedure in a prospective cohort study. Int J Surg. 2025 Jul 1;111(7):4211-4221. doi: 10.1097/JS9.0000000000002490. Ma X, Wang F, Wang G, Zhao M, Zheng Y, Guo Y, Wu J, Liu Y, Liu Y, He G, Ren L, Gong Z, Wang J, Chen L, Hu S, Chu Q, Li Z, Wu J, Li R, Zhang X, Shi Q, Lian H, Ye J. A surgical therapy for Alzheimer's disease with lymphaticovenular anastomosis. J Alzheimers Dis Rep. 2025 Oct 3;9:25424823251384244. doi: 10.1177/25424823251384244. Tang C, Zheng X, Li H, Wang B, Zheng Y, Song W, Wu A, Xin L, Zhang D, Yang R, Du S, He P , Li Y, Wu L, Wang X, Shi Q, Bernardes GJL. Deep cervical lymphatic-venous anastomosis in dementia: a clinical and mechanistic evaluation. Int J Surg. 2025 Dec 17. doi: 10.1097/JS9.0000000000004561. Wu C, Yuan J, Tian Y, Wang Y, He X, Zhao K, Huang J, Jiang R. Tauopathy after long-term cervical lymphadenectomy. Alzheimers Dement. 2025 Apr;21(4):e70136. doi: 10.1002/alz.70136. Jessup M, Iglesias NJ, Tadisina KK, Xu K, Mella-Catinchi J, Pinchuk L, Singh D, Tse DT, Nayak VV, Coelho PG. The emerging role of biomaterial applications in cerebral lymphatic surgical interventions: A narrative review. Biomater Biosyst. 2025 Aug 9;19:100117. doi: 10.1016/j.bbiosy.2025.100117. Hong JP , Chen WF, Nguyen DH, Xie Q. A Proposed Role for Lymphatic Supermicrosurgery in the Mana
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Effects of Restoring Lymphatic Drainage in Alzheimer's Disease: The LymphDAD Pilot Study
- ClinicalTrials.gov ID
- NCT07854327
- Acronym / sponsor ID
- LymphDAD / LymphDAD
- Conditions
- Alzheimer, Alzheimer Dementia (AD)
- Keywords
- Alzheimer Disease, Alzheimer Dementia, Lymphovenous Anastomosis, Cervical Lymphatic Drainage, Deep Cervical Lymphatic System, Glymphatic System, Meningeal Lymphatics, Lymphovenous Bypass
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- University of SienaUniversity, hospital or other
- Study start
- 1 Jul 2026 (actual)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 2 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
The 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.
Five 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.
Participants 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.
The 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.
Detailed description
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.
Emerging 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.
The 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.
All 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.
The 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.
Neuroimaging 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.
Assessments 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.
The 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cervical Lymphovenous Anastomosis (LVA) | Experimental | Procedure: Cervical lymphovenous anastomosis (LVA)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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of Alzheimer's disease according to NIA-AA 2024 criteria.
- Not eligible for other disease-modifying therapies.
- Ability to personally provide written informed consent after clinical evaluation -of decisional capacity.
Key exclusion criteria (13 listed)
- Coagulopathy or active infection of the head and neck region.
- Prior extensive cervical lymph node dissection or radiotherapy.
- Uncontrolled systemic disease or contraindication to general anesthesia.
- Participation in another interventional trial within the previous 3 months.
- Known hypersensitivity or allergy to indocyanine green.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Procedure or surgery | Cervical Lymphovenous Anastomosis (LVA) |
| Cervical lymphovenous anastomosis (LVA)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. | Procedure or surgery | Cervical Lymphovenous Anastomosis (LVA) |
Primary outcome
Change from baseline in plasma amyloid-beta concentrations
Time frame: Baseline, 1 month, and 6 months after LVA
Change from baseline in plasma amyloid-beta 42 (Aβ42) and amyloid-beta 40 (Aβ40) concentrations following cervical lymphovenous anastomosis (LVA).
Change from baseline in plasma phosphorylated tau concentrations
Time frame: Baseline, 1 month, and 6 months after LVA
Change from baseline in plasma phosphorylated tau 181 (p-tau181) and phosphorylated tau 217 (p-tau217) concentrations following cervical LVA.
Change from baseline in plasma NfL and GFAP concentrations
Time frame: Baseline, 1 month, and 6 months after LVA
Change from baseline in plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) concentrations following cervical LVA.
5 secondary outcomes
Change from baseline in Mini-Mental State Examination score
Time frame: Baseline to 3, 6, and 12 months after LVA
Change from baseline in Montreal Cognitive Assessment score
Time frame: Baseline to 3, 6, and 12 months after LVA
Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale score
Time frame: Baseline to 3, 6, and 12 months after LVA
Change from baseline in Neuropsychiatric Inventory score
Time frame: Baseline to 3, 6, and 12 months after LVA
Change from baseline in Clinical Dementia Rating score
Time frame: Baseline to 3, 6, and 12 months after LVA
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- BackgroundImholz C, Schaller C, Watson JA, Zurfluh CE, Grigorean A, Lindenblatt N. Robotic-assisted lymphovenous anastomosis to treat periorbital lymphedema and systematic review of lymphatic reconstruction of face and neck lymphedema. J Robot Surg. 2025 Jul 12;19(1):380. doi: 10.1007/s11701-025-02552-6. Xie Q, Pak CJ, Kwon J, Chao SC, Hong JP . Potential Role of Lymphovenous Bypass in Mitigating Alzheimer's Disease Dementia. Arch Plast Surg. 2025 Jul 23;52(4):247-252. doi: 10.1055/a-2627-9243. Chen JY, Zhao DW, Yin Y, Gui L, Chen X, Wang XM, Wang PB, Zuo CH, Lai ZP , Li C, Wang R, Xian JS, Chen Z, Feng H, Hu R. Deep cervical lymphovenous anastomosis (LVA) for Alzheimer's disease: microsurgical procedure in a prospective cohort study. Int J Surg. 2025 Jul 1;111(7):4211-4221. doi: 10.1097/JS9.0000000000002490. Ma X, Wang F, Wang G, Zhao M, Zheng Y, Guo Y, Wu J, Liu Y, Liu Y, He G, Ren L, Gong Z, Wang J, Chen L, Hu S, Chu Q, Li Z, Wu J, Li R, Zhang X, Shi Q, Lian H, Ye J. A surgical therapy for Alzheimer's disease with lymphaticovenular anastomosis. J Alzheimers Dis Rep. 2025 Oct 3;9:25424823251384244. doi: 10.1177/25424823251384244. Tang C, Zheng X, Li H, Wang B, Zheng Y, Song W, Wu A, Xin L, Zhang D, Yang R, Du S, He P , Li Y, Wu L, Wang X, Shi Q, Bernardes GJL. Deep cervical lymphatic-venous anastomosis in dementia: a clinical and mechanistic evaluation. Int J Surg. 2025 Dec 17. doi: 10.1097/JS9.0000000000004561. Wu C, Yuan J, Tian Y, Wang Y, He X, Zhao K, Huang J, Jiang R. Tauopathy after long-term cervical lymphadenectomy. Alzheimers Dement. 2025 Apr;21(4):e70136. doi: 10.1002/alz.70136. Jessup M, Iglesias NJ, Tadisina KK, Xu K, Mella-Catinchi J, Pinchuk L, Singh D, Tse DT, Nayak VV, Coelho PG. The emerging role of biomaterial applications in cerebral lymphatic surgical interventions: A narrative review. Biomater Biosyst. 2025 Aug 9;19:100117. doi: 10.1016/j.bbiosy.2025.100117. Hong JP , Chen WF, Nguyen DH, Xie Q. A Proposed Role for Lymphatic Supermicrosurgery in the Mana
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paolo Gennaro, Professor study chair
University of Siena, Department of Biotechnology
Domenico Plantone, Professor principal investigator
University of Siena, Department of Neurology
Federica Orsini, MD principal investigator
University of Siena, Department of Nuclear Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cervical lymphovenous anastomosis (LVA) in people with Alzheimer and Alzheimer Dementia (AD), run by University of Siena at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrea Frosolini, MD (3939447318 ext. 0039, andreafrosolini@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in plasma amyloid-beta concentrations (time frame: Baseline, 1 month, and 6 months after LVA). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07854327, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.