NCT07680660尚未招募不适用
A Multicenter Randomized Controlled Trial on the Efficacy and Safety of Cervical Lymph Vessel/Node-venous Anastomosis Combined With Donepezil Versus Donepezil Alone in the Treatment of Alzheimer's Disease
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University1 个研究点 分布在 1 个国家目标入组 216 人开始时间: 2026年7月15日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 216
- 试验地点
- 1
- 主要终点
- Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score at Month 12
研究概览
简要总结
This study employed a multicenter, randomized controlled trial (RCT) design to evaluate the efficacy and safety of deep cervical lymphatic/lymph node-venous anastomosis combined with oral donepezil compared to donepezil monotherapy in patients with Alzheimer's disease and moderate dementia. Participants were randomized using a central randomization system with stratified block design, with the study center and age group (50-64 years, 65-80 years) as stratification factors. While study participants and surgical investigators could not be blinded due to the nature of the intervention, efficacy assessors and imaging specialists remained blinded to ensure the objectivity and reliability of the findings. The intervention group received deep cervical lymphatic/lymph node-venous anastomosis (detailed surgical procedure is specified in the protocol) in combination with oral donepezil (5-10 mg/day), while the control group received oral donepezil alone. The total treatment and follow-up period was 18 months, with assessments conducted at baseline, 1 week, 1, 3, 6, 12, and 18 months post-operation. These included neuropsychological evaluations (MMSE, MoCA, CDR, BADL, IADL, NPI, AES), neuroimaging (MRI, PET, ultrasound), fluid biomarker analyses (CSF and blood levels of Aβ, Tau, neuroinflammatory factors, etc.), and safety monitoring. The primary efficacy endpoint was the change in CDR-SB score at 12 months post-treatment. Secondary endpoints included changes in multiple cognitive scales, neuroimaging metrics, and biomarkers at 18 months. Safety indicators encompassed adverse event recording, vital signs, and laboratory tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient or guardian signs the informed consent form;
- •Age 50-80 years (≥50 years, ≤80 years), male or female;
- •The first diagnosis is Alzheimer's disease with dementia;
- •MMSE score ≤24;
- •Positive β-amyloid protein PET imaging findings;
- •HAMD score ≤17;
- •Hachinski score ≤7;
- •No AD-related drug treatment has been received within the past 1 month;
- •ASA grade 1-3 (≥ grade 1, ≤ grade 3);
- •CDR-SB score of 9.5-15.5.
排除标准
- •Presence of contraindications to MRI, ICG angiography, or PET scan;
- •Presence of contraindications to lumbar puncture;
- •Severe heart disease or unstable hemodynamic status;
- •Severe lung disease, including severe obstructive, restrictive, or mixed ventilatory dysfunction, or acute inflammation within 3 months;
- •Hepatic insufficiency, AST or ALT >3 times the upper limit of normal;
- •Renal insufficiency, GFR <60 mL/min or need for blood purification treatment;
- •MRI indicates active or acute intracranial lesions, including intracranial infection, space-occupying lesions, major hemorrhage, and ≥4 lobar microbleeds, etc.;
- •History of cerebral hemorrhage or cerebral infarction with severe residual neurological dysfunction;
- •Blood diseases, bleeding/coagulation disorders, coagulation dysfunction;
- •Abnormal thyroid function;
- •Moderate or severe stenosis of intracranial or cervical vessels with severe residual neurological dysfunction;
- •Severe hypertension not effectively controlled, systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg;
- •The disease requires systemic use of steroids;
- •Drug addiction (including alcohol, narcotics, and alcohol dependence);
- •Severe infectious diseases, including HIV positivity, severe infection, etc.;
- •Severe psychiatric disease or potential suicide risk;
- •Within 3 years after radical surgery for malignant tumor;
- •Participation in other interventional clinical trials within the past three months;
- •In the physician's judgment, poor compliance, inability to complete, or unwillingness to cooperate with regular postoperative follow-up;
- •Other circumstances that the physician considers unsuitable for this clinical trial;
- •Anti-Aβ monoclonal antibody treatment has been received within half a year;
- •Previous neck surgery.
研究组 & 干预措施
Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group
Experimental
干预措施: Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil (Procedure)
Oral donepezil group
Active Comparator
干预措施: Oral treatment with donepezil (Drug)
Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group
Experimental
干预措施: Oral treatment with donepezil (Drug)
结局指标
主要结局
Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score at Month 12
时间窗: Baseline and Month 12
The Clinical Dementia Rating-Sum of Boxes is a clinician-rated measure of dementia severity. The score ranges from 0 to 18, with higher scores indicating greater impairment and more severe dementia. The outcome measure is the change from baseline to Month 12. The scale will be administered face to face by trained evaluators blinded to treatment assignment, and results will be reviewed by an independent endpoint adjudication committee.
次要结局
- Concentration of Phosphorylated Tau 181 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Change From Baseline in Montreal Cognitive Assessment Score at Month 18(Baseline and Month 18)
- Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score at Month 18(Baseline and Month 18)
- Change From Baseline in Mini-Mental State Examination Score at Month 18(Baseline and Month 18)
- Change From Baseline in 18-item Apathy Evaluation Scale Score at Month 18(Baseline and Month 18)
- Change From Baseline in Neuropsychiatric Inventory Total Score at Month 18(Baseline and Month 18)
- Change From Baseline in Basic Activities of Daily Living Score at Month 18(Baseline and Month 18)
- Change From Baseline in Instrumental Activities of Daily Living Score at Month 18(Baseline and Month 18)
- Change From Baseline in PET Imaging Measures at Month 18(Baseline and Month 18)
- Change From Baseline in Brain Volumetric MRI Measures at Month 18(Baseline and Month 18)
- Change From Baseline in Glymphatic System-Related MRI Measures at Month 18(Baseline and Month 18)
- Change From Baseline in Internal Jugular Vein Diameter on Ultrasound at Month 18(Baseline and Month 18)
- Change From Baseline in External Jugular Vein Diameter on Ultrasound at Month 18(Baseline and Month 18)
- Change From Baseline in Maximum Jugular Vein Flow Velocity on Ultrasound at Month 18(Baseline and Month 18)
- Histopathological Findings in Intraoperatively Collected Lymph Node Tissue(During surgery)
- Concentration of Phosphorylated Tau 217 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Amyloid-Beta 42 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Amyloid-Beta 40 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Neurofilament Light Chain in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Glial Fibrillary Acidic Protein in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-1 Alpha in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-1 Beta in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-8 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Tumor Necrosis Factor Alpha in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-12 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-6 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interferon Gamma in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-17A in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-4 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-10 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-1 Receptor Antagonist in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Transforming Growth Factor Beta in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Change From Baseline in Cerebrospinal Fluid P-tau181 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid Total Tau Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid Aβ42 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid Aβ40 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid Aβ42/Aβ40 Ratio at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid BD-tau Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid GFAP Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid NfL Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid pTau217 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-1α Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-1β Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-8 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid TNF-α Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-12 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-6 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IFN-γ Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-17A Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-4 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-10 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-1ra Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid TGF-β Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma P-tau181 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma Total Tau Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma Aβ42 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma Aβ40 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma Aβ42/Aβ40 Ratio at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma BD-tau Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma GFAP Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma NfL Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma pTau217 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-1α Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-1β Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-8 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma TNF-α Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-12 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-6 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IFN-γ Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-17A Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-4 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-10 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-1ra Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma TGF-β Level at Month 18(Baseline and Month 18)
- Concentration of Interleukin-2 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-12 p70 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-17 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interleukin-5 in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Concentration of Interferon Alpha in Intraoperatively Collected Lymphatic Fluid(During surgery)
- Change From Baseline in Cerebrospinal Fluid IL-2 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-12p70 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-17 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid IL-5 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Cerebrospinal Fluid Interferon Alpha Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-2 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-12p70 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-17 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma IL-5 Level at Month 18(Baseline and Month 18)
- Change From Baseline in Plasma Interferon Alpha Level at Month 18(Baseline and Month 18)
研究者
研究点 (1)
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