Deep Cervical LymphatIc-Venous Anastomosis for Alzheimer's Disease

Официальное название

Deep Cervical LymphatIc-Venous Anastomosis for Alzheimer's Disease (CLIVA-AD): a Prospective, Single-center, Randomized, Double Blinded Trial

Обзор

Lymphaticovenous anastomosis (LVA) is a microsurgical technique that involves anastomosing fine lymphatic vessels with adjacent veins to reestablish lymphatic drainage pathways. It is used in the treatment of lymphedema-related conditions and is characterized by minimal invasiveness and rapid recovery. Based on findings from animal studies, some physicians in China have attempted deep cervical lymphatic-venous anastomosis to improve intracranial lymphatic drainage in patients with Alzheimer's disease (AD). Most studies, including those from our center, have observed early postoperative improvements in various domains such as mood, memory, executive function, and communication abilities in the majority of patients. However, these symptomatic improvements are not sustained. The reasons for the early improvements remain unclear. Are they due to enhanced lymphatic drainage resulting from the surgery itself, or are they attributable to other factors such as anesthetic effects, vascular release, or modulation of sympathetic nerves? Therefore, it is necessary to conduct a randomized controlled trial with a sham surgery group to clarify the causes of early clinical symptom improvements. Based on this, this project aims to carry out a prospective, single-center, randomized double-blind controlled study to evaluate whether the early symptomatic improvements following deep cervical LVA in AD patients are attributable to the surgical intervention itself or to other aspects of the procedure.

Вмешательства

• Процедура deep cervical lymphaticovenous anastomosis
  patients will receive deep cervical lymphaticovenous anastomosis

Первичные конечные точки

• Changes in Montreal Cognitive Assessment (MoCA) score [Срок оценки: 4±1 days]
• Changes in Mini-mental State Examination (MMSE) score [Срок оценки: 4±1 days]
• Changes in Barthel index (BI) [Срок оценки: 4±1 days]
• Changes in Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus) [Срок оценки: 4±1 days]

Вторичные конечные точки (5)

• Changes in Montreal Cognitive Assessment (MoCA) score [Срок оценки: 90±7 days; 180±15 days; 270±20 days]
• Changes in Mini-mental State Examination (MMSE) score [Срок оценки: 90±7 days; 180±15 days; 270±20 days]
• Changes in Barthel index (BI) [Срок оценки: 90±7 days; 180±15 days; 270±20 days]
• Changes in Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus) [Срок оценки: 90±7 days; 180±15 days; 270±20 days]
• Severe adverse events [Срок оценки: Perioperative period]

Критерии участия

Критерии включения

• Age 50-80 years (inclusive), regardless of gender.
• Meeting the diagnostic criteria for Mild Cognitive Impairment or mild to moderate dementia due to Alzheimer's disease (according to the 2024 AA clinical diagnostic criteria for AD-related dementia).
• Disease duration of 6 months or longer, with no clinical improvement after 3 months or more of conservative treatment.
• MMSE score: 12-26.
• Biomarker confirmation of AD: positive Aβ-PET and tau-PET, or positive cerebrospinal fluid biomarkers.
• Having a reliable caregiver (providing companionship for ≥3 hours per day).
• Signed written informed consent from the patient or legally authorized representative.

Критерии исключения

• Contraindications to MRI, ICG angiography, or PET.
• Contraindications to surgery or anesthesia, such as coagulation disorders (platelet count <100×10⁹/L, INR >1.7).
• Comorbid major organ dysfunction, such as reduced left ventricular ejection fraction, severe hepatic or renal insufficiency (AST or ALT >3 times the upper limit of normal; eGFR <30 mL/min/1.73m²).
• Intracranial structural lesions indicated by MRI, including brain tumors, cerebral infarction, intracranial hemorrhage, aneurysms, arteriovenous malformations, hydrocephalus, etc.
• MRI findings suggestive of significant cerebral small vessel disease features: more than one lacunar infarction in the deep white matter and periventricular regions and/or white matter hyperintensity (WMH) with a Fazekas grade >2, or the presence of ≥4 cerebral microbleeds.
• Other causes of dementia, such as hypothyroidism or vitamin B12 deficiency.
• Drug/alcohol addiction.
• Severe psychiatric illness or suicide risk.
• Comorbid medical conditions with a life expectancy of less than 1 year.
• Participation in another interventional trial within the past 3 months.
• Poor compliance or judged by the investigator as unsuitable for participation.
• Patients receiving therapy with Lecanemab or Donanemab.
• Other conditions that the researcher deems unsuitable for participation in this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Neurology, General Hospital of Northern Theater Command — Шэньян

Идентификаторы

NCT: NCT07294885 · Y (2025) 250

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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