Restoring Cervical Lymphatic Drainage in Alzheimer's Disease

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

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.

Study 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 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

Primary outcome measure(s)

• Change from baseline in plasma amyloid-beta concentrations — 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 — 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 — 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.

Trial sites (1)

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