Prospective Single-Arm Safety Study of Cervical LVA in AD Patients

NCT07458620 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 202500102A0
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Official Title Prospective Single-Arm Safety Study of Cervical Lymphaticovenular Anastomosis (LVA) in Patients with Alzheimer's Disease Purpose of the Study Researchers are conducting this study to see if a minimally invasive microsurgery, called Cervical Lymphaticovenular Anastomosis (LVA), is safe for people with Alzheimer's Disease. How the Surgery Works Alzheimer's Disease is linked to the buildup of metabolic waste products (certain proteins) in the brain. Recent medical discoveries show that these wastes normally drain through small channels in the neck into the blood system. In this study, surgeons will use high-powered microscopes to connect these drainage channels (lymphatic vessels) in the neck directly to small nearby veins. The goal is to create a "detour" that helps the brain clear out these harmful proteins more effectively. What to Expect Safety First: The main goal is to find out if the surgery is safe and well-tolerated by patients. The Procedure: The surgery is performed under general anesthesia and typically takes 4 to 6 hours. It involves small (about 5 cm) incisions on both sides of the neck. Follow-up: Participants will be monitored for at least 12 months. Researchers will use memory tests, brain scans (MRI and PET), and blood tests to see if the surgery helps with daily activities or slows down memory loss.

Conditions

Alzheimer's Disease (AD)

Keywords

Alzheimer's Disease (AD); Neurodegenerative Diseases; Dementia; Lymphaticovenular Anastomosis (LVA); Supermicrosurgery; Cervical Lymphatic Bypass; Glymphatic System Clearance; Meningeal Lymphatic System; Amyloid-beta (Aβ) Drainage; Tau Protein Clearance; CSF; Deep Cervical Lymph Nodes (dCLNs); Amyloid-PET Imaging; Indocyanine Green (ICG) Lymphography

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (Safety and Feasibility)

  Assessment of the safety and feasibility of bilateral cervical supermicrosurgical lymphaticovenular anastomosis (LVA). Safety is evaluated by the frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring from the start of the surgical procedure through the 1-month post-operative follow-up period. Events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  From the start of surgery up to 1 month post-operation.

Secondary Outcomes (5)

• Change from Baseline in Mini-Mental State Examination (MMSE) Score

  Baseline and 6 months post-operation

• Change from Baseline in Clinical Dementia Rating (CDR)

  Baseline and 6 months post-operation.

• Changes from Baseline in Cognitive Abilities Screening Instrument (CASI)

  Baseline and 6 months post-operation.

• Change in Brain Amyloid-beta Deposition via PET Scan

  Baseline and post-operation.

• Change in Plasma Neurodegenerative Biomarker Levels

  Baseline and post-operation.

Study Arms (1)

Single-Arm Cervical LVA Intervention Supporting Context Arm Type

EXPERIMENTAL

The single experimental arm involves bilateral cervical supermicrosurgical Lymphaticovenular Anastomosis (LVA). Participants undergo a surgical procedure where high-power microscopy is used to identify cervical lymphatic vessels. These vessels are then microsurgically connected (anastomosed) to adjacent small veins to create an extra-cranial bypass. The intervention utilizes Indocyanine Green (ICG) fluorescence imaging to precisely map the lymphatic drainage pathways in the neck. The primary goal of this bypass is to enhance the clearance of metabolic waste-specifically Amyloid-beta and tau proteins-from the brain by facilitating their drainage from the glymphatic and meningeal lymphatic systems into the systemic venous circulation. This trial evaluates the safety and feasibility of this approach in mitigating the progression of Alzheimer's Disease.

Procedure: Supermicrosurgical Lymphaticovenular Anastomosis (LVA)

Interventions

Supermicrosurgical Lymphaticovenular Anastomosis (LVA) PROCEDURE

This intervention is uniquely distinguished by its use of supermicrosurgery to perform bilateral cervical Lymphaticovenular Anastomosis (LVA) as a direct physiological treatment for Alzheimer's Disease. Unlike traditional pharmacological trials that target protein production or aggregation, this surgical approach focuses on the mechanical clearance of metabolic waste. A key technical differentiator is the specific targeting of neck lymph nodes using Indocyanine Green (ICG) fluorescence to map the drainage pathway of cerebrospinal fluid. This allows for a precise, "super-microsurgical" bypass (connecting vessels often \<0.8mm) in the neck. This method aims to bypass potential blockages in the aging dCLNs (deep cervical lymph nodes), directly enhancing the outflow of Amyloid-beta and Taufrom the glymphatic and meningeal systems into the venous circulation.

Single-Arm Cervical LVA Intervention Supporting Context Arm Type

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Alzheimer's Disease: Participants must have a confirmed diagnosis of Alzheimer's Disease as evaluated by a neurologist and a psychiatrist at the hospital.
• Positive Amyloid-PET Scan: The result of a \[18F\] Florbetapir (Amyloid-PET) scan must be positive, indicating the presence of amyloid plaques in the brain.
• Willingness to Consent: Participants or their legal representatives must be willing to sign a written informed consent form.
• Participants must be adults aged 18 years or older

You may not qualify if:

• Lack of Informed Consent: Potential participants are excluded if they are unable to exercise autonomy and informed consent cannot be obtained from a legal representative or authorized person.
• Prior Surgical History: Individuals who have previously undergone neck lymphatic dissection, nasopharyngeal surgery, or intracranial surgery are excluded.
• Concurrent Medical Conditions: The trial excludes persons with thyroid disease or chronic heart failure.
• Specific Allergies: Candidates with a history of allergies to shellfish or iodine are excluded due to the use of Indocyanine Green (ICG) during the procedure.
• Unresolved Concerns: Anyone who has doubts about the trial and cannot receive satisfactory answers is excluded.
• Anesthesia Risks: Individuals deemed medically unfit for general anesthesia-for example, those with severe cardiopulmonary insufficiency or a history of specific anesthetic drug allergies-are ineligible.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

Location

Related Publications (2)

• Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jul 16;523(7560):337-41. doi: 10.1038/nature14432. Epub 2015 Jun 1.

  PMID: 26030524 BACKGROUND

• Hong JP, Chen WF, Nguyen DH, Xie Q. A Proposed Role for Lymphatic Supermicrosurgery in the Management of Alzheimer's Disease: A Primer for Reconstructive Microsurgeons. Arch Plast Surg. 2025 Jan 30;52(2):96-103. doi: 10.1055/a-2513-4313. eCollection 2025 Mar.

  PMID: 40083619 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Neurodegenerative Diseases; Dementia; Plaque, Amyloid

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Johnson Chia-Shen Yang,, MD, PhD

CONTACT

+886-975056253; johnson.c.yang@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2026
• First Posted: March 9, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)