Restoring Cervical Lymphatic Drainage in Alzheimer's Disease
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorUniversity of Siena
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Cervical lymphovenous anastomosis (LVA)
Procedure/SurgeryMicrosurgical 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/SurgeryMicrosurgical 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.
Treatment groups
5 Participants
are divided into 1 treatment groupGroup A: Cervical Lymphovenous Anastomosis (LVA)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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).
Time frame
Baseline, 1 month, and 6 months after LVA2
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.
Time frame
Baseline, 1 month, and 6 months after LVA3
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.
Time frame
Baseline, 1 month, and 6 months after LVASecondary outcomes
1
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.
Time frame
Baseline to 3, 6, and 12 months after LVA2
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.
Time frame
Baseline to 3, 6, and 12 months after LVA3
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.
Time frame
Baseline to 3, 6, and 12 months after LVA4
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.
Time frame
Baseline to 3, 6, and 12 months after LVAOther outcomes
1
Change from baseline in hippocampal volume on magnetic resonance imaging
Change from baseline in automated hippocampal volume measured on structural magnetic resonance imaging (MRI).
Time frame
Baseline and 6 months after LVA2
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).
Time frame
Baseline and 6 months after LVA3
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).
Time frame
Baseline and 6 months after LVA4
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).
Time frame
Baseline and 6 months after LVASponsors and contacts
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Source ClinicalTrials.gov