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

Официальное название

Prospective Single-Arm Safety Study of Cervical Lymphaticovenular Anastomosis (LVA) in Patients With Alzheimer's Disease

Обзор

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.

Подробное описание

Official Title Prospective Single-Arm Safety Study of Cervical Lymphaticovenular Anastomosis (LVA) in Patients with Alzheimer's Disease

Scientific Rationale Neurodegenerative diseases like Alzheimer's (AD) are characterized by the misfolding and accumulation of proteins such as Amyloid-beta and Tau. The glymphatic and meningeal lymphatic systems serve as the primary pathways for clearing these metabolic wastes from the central nervous system into the deep cervical lymph nodes. This study investigates whether enhancing this drainage via supermicrosurgical lymphaticovenular anastomosis (LVA) can reduce intracranial protein burden and systemic oxidative stress.

Study Design and Intervention This is a prospective, single-arm safety study. Participants undergo bilateral cervical LVA. Using Indocyanine Green (ICG) fluorescence lymphography for navigation, lymphatic vessels in the neck are identified and anastomosed to adjacent small veins to facilitate lymph drainage into the venous circulation.

Safety Monitoring and Data Integrity Primary Safety Endpoint: The study defines safety as a Serious Adverse Event (SAE) rate of ≤10% within the first month post-operation. Events are graded using CTCAE v5.0.

Independent Oversight: To ensure objectivity, cognitive and behavioral assessments (including MMSE, CDR, and CASI) are conducted by clinical psychologists who are not members of the core research team.

External Auditing: An independent Clinical Research Organization (CRO) has been contracted to perform four periodic audits to verify data accuracy and GCP compliance.

Exploratory Objectives

The study will track longitudinal changes in:

Fluid Biomarkers: Plasma levels of Amyloid-beta 40/42, p-Tau 217, GFAP, and Nf-L at baseline, 1, 6, and 12 months.

Neuroimaging: Amyloid-PET and FDG-PET scans at baseline and 12 months to evaluate protein deposition and metabolic activity.

Clinical Outcomes: Changes in cognitive scores (CDR, MMSE, CASI, NPI) from baseline to 6 months post-surgery.

Вмешательства

• Процедура Supermicrosurgical Lymphaticovenular Anastomosis (LVA)
  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 t

Первичные конечные точки

• Incidence of Treatment-Emergent Adverse Events (Safety and Feasibility) [Срок оценки: From the start of surgery up to 1 month post-operation.]

Вторичные конечные точки (5)

• Change from Baseline in Mini-Mental State Examination (MMSE) Score [Срок оценки: Baseline and 6 months post-operation]
• Change from Baseline in Clinical Dementia Rating (CDR) [Срок оценки: Baseline and 6 months post-operation.]
• Changes from Baseline in Cognitive Abilities Screening Instrument (CASI) [Срок оценки: Baseline and 6 months post-operation.]
• Change in Brain Amyloid-beta Deposition via PET Scan [Срок оценки: Baseline and post-operation.]
• Change in Plasma Neurodegenerative Biomarker Levels [Срок оценки: Baseline and post-operation.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Тайвань · 1 центр

• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City

Публикации

• 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
• 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

Идентификаторы

NCT: NCT07458620 · 202500102A0

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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