Effect of Cervical Lymphaticovenous Anastomosis and Cervical Lymph Node to Vein Anastomosis for the Patient With Intracranial Lymphatic Circulation Disorder
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Change in Global Deterioration Scale (GDS) Score
研究概览
简要总结
This study is a single-center, prospective clinical trial designed to evaluate the therapeutic effects of lymphaticovenular anastomosis (LVA) and lymph node-venous anastomosis (LNVA) in patients with intracranial lymphatic circulation disorders. Following voluntary written informed consent, screening assessments will be performed in accordance with the clinical trial protocol. Eligibility will be determined based on the predefined inclusion and exclusion criteria, and eligible subjects will be enrolled in the study. Enrolled participants will undergo cognitive function assessments at baseline (pre-surgery) and at 1, 3, 6, 9, 12, 18, and 24 months postoperatively for follow-up. Cognitive evaluations will not be additionally performed for research purposes but will be conducted in accordance with the existing clinical care schedule and standard treatment guidelines.
详细描述
There are several theories regarding the causes of mild cognitive impairment (MCI) and dementia, and one of the commonly proposed mechanisms involves the accumulation of amyloid, a metabolic waste product, within the brain parenchyma. This accumulation is thought to result from impaired clearance of waste from the brain. Accordingly, impaired function of the brain's waste drainage system may contribute to the development of cognitive symptoms.
Because waste clearance from the brain occurs through lymphatic pathways, dysfunction of lymphatic circulation has been identified as an important contributing factor to MCI and dementia. However, due to the minute diameter of lymphatic vessels-typically less than 1 mm-direct therapeutic interventions targeting lymphatic function have long remained unexplored.
Recent advances in supermicrosurgical techniques have enabled procedures on lymphatic vessels as small as 0.2-0.3 mm, leading to the development of novel treatments for lymphatic circulation disorders. For example, patients with upper or lower extremity lymphedema, a representative condition of lymphatic dysfunction, have shown significant improvement following lymphaticovenular anastomosis (LVA) or lymph node-venous anastomosis (LNVA).
Lymphedema results from obstruction or damage to lymphatic pathways, causing the accumulation of lymphatic fluid in tissues. LVA and LNVA are microsurgical procedures that create new bypass routes by connecting lymphatic vessels or lymph nodes directly to adjacent veins, thereby allowing lymphatic fluid to drain into the venous system and re-enter systemic circulation. These procedures have been performed for more than two decades, with excellent therapeutic outcomes reported over the past five years. At Asan Medical Center, more than 100 such procedures are successfully performed annually.
Furthermore, based on the same principle applied in limb lymphedema, recent case-level studies have suggested that performing LVA or LNVA in lymphatic pathways or lymph nodes responsible for cerebral waste clearance may improve degenerative neurological conditions, including Alzheimer's disease. Based on this accumulated knowledge and surgical expertise, cervical lymphaticovenular anastomosis and cervical lymph node-venous anastomosis will be performed to connect lymphatic vessels and lymph nodes involved in cerebral lymphatic drainage to adjacent veins.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 19 years or older who are diagnosed with intracranial lymphatic circulation disorder based on neurological evaluation.
- •Global Deterioration Scale (GDS) score between 3 and 5 at screening.
- •Diagnosis of Alzheimer's disease confirmed by amyloid PET-CT or CSF amyloid testing, showing amyloid accumulation associated with lymphatic circulation disorder.
- •Able to provide written informed consent to participate in the study voluntarily.
排除标准
- •Unable to undergo follow-up evaluation for at least 12 months after surgery.
- •Diagnosed with vascular dementia.
- •Presence of structural brain disease other than intracranial lymphatic circulation disorder.
- •Known hypersensitivity to indocyanine green (ICG).
- •Uncontrolled systemic medical conditions such as severe cardiopulmonary, renal, hepatic, or endocrine disorders.
- •History of previous neck surgery.
- •Refusal to participate or failure to provide informed consent.
- •Determined by the principal investigator to be unsuitable for participation due to any other clinical reason.
研究组 & 干预措施
Surgical Intervention Group
Participants in this group will undergo cervical lymphaticovenous anastomosis (LVA) and cervical lymph node-to-vein anastomosis (LNVA).
The procedure connects cervical lymphatic vessels and lymph nodes to adjacent veins to facilitate lymphatic drainage from the brain and reduce amyloid accumulation associated with intracranial lymphatic circulation disorder in patients with Alzheimer's disease.
干预措施: Cervical Lymphaticovenous and Lymph Node-to-Vein Anastomosis (Procedure)
Control Group
Participants in this group will receive standard medication therapy only, following the hospital's routine treatment guidelines for Alzheimer's disease.
结局指标
主要结局
Change in Global Deterioration Scale (GDS) Score
时间窗: From preoperative baseline to postoperative Months 1, 3, 6, 9, 12, 18, and 24
Cognitive decline will be assessed using the Global Deterioration Scale (GDS). The GDS score ranges from 1 to 7, with higher scores indicating more severe cognitive impairment. The outcome measure is the change in GDS score from baseline to postoperative follow-up visits. Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.
Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
时间窗: Preoperative baseline and postoperative Month 12
Dementia severity will be evaluated using the Clinical Dementia Rating - Sum of Boxes (CDR-SB). CDR-SB scores range from 0 to 18, with higher scores indicating more severe cognitive impairment The outcome measure is the change in CDR-SB score from baseline to postoperative follow-up visits. Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.
Change in Korean Mini-Mental State Examination (K-MMSE) Score
时间窗: From preoperative baseline to postoperative Months 1, 3, 6, 9, 12, 18, and 24
Cognitive function will be assessed using the Korean Mini-Mental State Examination (K-MMSE). K-MMSE scores range from 0 to 30, with higher scores indicating better cognitive function. The outcome measure is the change in K-MMSE scores from the preoperative baseline to 12 months after surgery. Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.
Change in Montreal Cognitive Assessment (MoCA) Score
时间窗: Preoperative baseline; postoperative Day 4; Months 1, 3, 6, 9, 12, 18, and 24
Cognitive performance will be assessed using the Montreal Cognitive Assessment (MoCA). MoCA scores range from 0 to 30, with higher scores indicating better cognitive performance. The outcome measure is the change in MoCA scores from the preoperative baseline to 12 months after surgery. Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.
Change in Seoul Neuropsychological Screening Battery (SNSB) Score
时间窗: Preoperative baseline; postoperative Months 6, 12, and 24
Cognitive function will be assessed using the Seoul Neuropsychological Screening Battery (SNSB), a comprehensive neuropsychological test battery evaluating multiple cognitive domains including attention, language, visuospatial function, memory, and executive function. SNSB provides domain-specific and composite scores, with higher scores generally indicating better cognitive performance, depending on the specific subtest. Score ranges differ across subtests within the SNSB. The outcome measure is the change in SNSB scores from the preoperative baseline to postoperative follow-up assessments. Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.
次要结局
- Incidence of Surgical Complications and Adverse Events(From the day of surgery through postoperative Month 24)
- Change in Amyloid-Related Blood Biomarkers(Preoperative baseline; postoperative Months 1, 3, 6, 12, and 24)
- Change in Blood Biomarkers of Neurodegeneration(Preoperative baseline; postoperative Months 1, 3, 6, 12, and 24)
研究者
Hong Joonpio
Principal Investigator
Asan Medical Center