The Efficacy and Safety of Deep Cervical LYMphatic-Venous Anastomosis for Moderate Alzheimer's Disease: A Multicenter, Prospective, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 296
- 试验地点
- 1
研究概览
简要总结
This is a multicenter, prospective, open-label, endpoint-blinded randomized controlled clinical study. We aim to evaluate the safety and efficacy of deep cervical lymphovenous anastomosis (LVA) combined with routine treatment for patients with moderate Alzheimer's disease, compared with routine treatment alone.
A total of 296 eligible participants aged 50 to 80 years with moderate Alzheimer's disease will be enrolled and randomly divided into two groups at a 1:1 ratio. One group will receive deep cervical lymphovenous anastomosis plus standard routine treatment, while the other group will only receive standard routine treatment for Alzheimer's disease.
All participants will be followed up for 12 months after randomization. We will assess cognitive function using MMSE and CDR-SB scales, evaluate caregiver burden via ZBI scale, and detect changes in Alzheimer's disease related biomarkers including blood amyloid-beta and tau protein, as well as Aβ-PET imaging indicators. The main goal is to observe whether this surgical procedure can improve patients' neurological function and clear abnormal protein deposits in the brain, and confirm its long-term safety.
This study strictly follows ethical principles. Every participant or their legal representative will sign a written informed consent before enrollment. During the whole study period, we will closely monitor all adverse events to ensure the safety of participants.
详细描述
Study Design and Objectives This is an interventional, multicenter, randomized, parallel-group, open-label and endpoint-blinded clinical trial. The primary objective is to verify the efficacy and safety of deep cervical lymphovenous anastomosis (LVA) in patients with moderate Alzheimer's disease. The secondary objectives include analyzing the changes of cognitive function, caregiver burden and cerebral amyloid-beta deposition within 12 months after intervention, and exploring the variation characteristics of peripheral blood biomarkers.
Study Population Eligible participants are patients diagnosed with probable Alzheimer's dementia consistent with 2011 NIA-AA clinical criteria and 2018 NIA-AA biomarker framework. Inclusion criteria: age 50 to 80 years; MMSE score between 10 and 20 points (moderate cognitive impairment); progressive cognitive decline for more than 6 months; no clinical improvement after more than six months of drug treatment; having a designated companion who can accompany follow-up and provide informed consent. Subjects with severe organ dysfunction, recent intracranial injury, drug allergy to study related reagents, PET contraindications or other severe mental disorders will be excluded.
Intervention and Control Measures Participants are randomly assigned to two groups by EDC system at a 1:1 ratio. Intervention group: Bilateral deep cervical lymphovenous anastomosis plus conventional symptomatic treatment for Alzheimer's disease. The operation is performed under surgical microscope with indocyanine green (ICG) lymphatic tracing technology. Postoperative routine anti-inflammatory treatment and rehabilitation training will be conducted.
Control group: Receive only standard drug treatment and routine rehabilitation training for Alzheimer's disease, without surgical intervention.
Evaluation Indicators and Time Points The primary outcome measure is the change of CDR-SB score from baseline to 12 months after randomization. Secondary outcome measures include changes in CDR-SB score at 1 month and 6 months, changes in MMSE and ZBI scores at 1, 6 and 12 months, and changes of Aβ-PET Centiloid value at 12 months. Exploratory indicators cover peripheral blood Aβ42, Aβ40, Aβ42/40 ratio, t-tau, p-tau and other biomarkers at each follow-up time point.
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)
盲法说明
Participants, care providers and investigators are aware of group allocation. Besides outcomes assessors, statistical analysts are also masked throughout the trial to minimize bias.
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
- •Aged 50 to 80 years old, male or female.
- •Clinically diagnosed with moderate probable Alzheimer's disease according to the NIA-AA criteria.
- •Baseline Mini-Mental State Examination (MMSE) score between 10 and 20 points.
- •Clinical cognitive decline duration of at least 6 months.
- •Stable routine anti-dementia drug treatment for more than 6 months without obvious clinical improvement.
- •Able to complete neuropsychological scale assessments, blood biomarker detection and Aβ-PET examination.
- •Have a reliable caregiver who can accompany follow-up visits and assist in completing evaluations.
- •The participant or legal surrogate voluntarily signs the written informed consent.
排除标准
- •Severe cardiac, hepatic, renal, respiratory or hematopoietic system dysfunction unable to tolerate surgery or anesthesia.
- •A history of intracranial surgery, severe craniocerebral trauma, stroke, brain tumor or other central nervous system diseases.
- •Other types of dementia, including vascular dementia, frontotemporal dementia, Lewy body dementia, or mixed dementia.
- •Psychiatric disorders requiring long-term medication that may affect cognitive assessment results.
- •Contraindications for PET imaging or contrast agent allergy.
- •Active infection, malignant tumor or severe wasting disease.
- •Pregnancy or breastfeeding status.
- •Participation in other interventional clinical trials within 3 months before enrollment.
- •Poor compliance or inability to complete scheduled follow-up.
- •Any other condition judged inappropriate for enrollment by the investigator.
研究者
Rong Hu, MD
Principal Investigator, Chief Physician, Neurosurgeon
Southwest Hospital, China