Prospective Single-Arm Safety Study of Cervical Lymphaticovenular Anastomosis (LVA) in Patients With Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety and Feasibility)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Single-Arm Cervical LVA Intervention Supporting Context Arm Type
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.
干预措施: Supermicrosurgical Lymphaticovenular Anastomosis (LVA) (Procedure)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety and Feasibility)
时间窗: From the start of surgery up to 1 month post-operation.
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.
次要结局
- 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.)