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Evaluating the Effects of Restoring Lymphatic Drainage in Alzheimer's Disease: The LymphDAD Pilot Study

Status: Recruiting
Location: See location...
Intervention Type: Procedure
Study Type: Interventional
Study Phase: Not Applicable
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
Participation Requirements
Sex: All
Healthy Volunteers: f
View:

• 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.

Locations
Other Locations
Italy
Azienda Ospedaliera Universitaria Le Scotte
RECRUITING
Siena
Contact Information
Primary
Andrea Frosolini, MD
andreafrosolini@gmail.com
3939447318
Backup
Carlo Manco, MD
carlooo95.CM@gmail.com
3460221117
Time Frame
Start Date: 2026-07-01
Estimated Completion Date: 2028-12-31
Participants
Target number of participants: 5
Treatments
Experimental: 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.
Related Therapeutic Areas
Sponsors
Leads: University of Siena

This content was sourced from clinicaltrials.gov