Cervical Lymphatico-Venous Bypass for Treatment of Alzheimer's Disease - Proof of Concept Study (CLyVeB-AD-1 Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Safety: Number of treatment-related adverse events
研究概览
简要总结
Alzheimer's disease (AD), one of the most common causes of dementia in Singapore and the developed world, is a neurodegenerative disorder with high socioeconomic impact. Accumulation of neurotoxic proteins (ie. amyloid, tau) are purported to lead to neuroinflammation, synaptic dysfunction and cognitive decline. The available pharmacotherapy provide limited symptomatic control, modest effect on disease progression with significant risk of side effects. Patients with AD eventually run out of effective pharmacotherapy and deteriorate.
Recent evidence implicated the glymphatic system, meningeal lymphatics of the brain, and downstream drainage to the cervical lymphatic system in the accumulation of neurotoxic proteins in AD. This presented the opportunity for extra-cranial intervention, and has since been demonstrated in preclinical models. Based on these development, Xie and colleagues pioneered the deep cervical lymph node to venous bypass (DCLNV-BP) procedure with very promising early outcomes. The observed improvement had been attributed to enhanced clearance of the neurotoxic proteins. Knowledge gap and clinical equipoise remain, and clinical trials are required to understand the safety, mechanism of action, patient selection, and long-term outcomes.
In this proof of concept study, the investigators aim to assess safety and preliminary efficacy of DCLNV-BP in AD. An approach using objective clinical assessments, biomarkers and neuroimaging, to assess safety, evaluate preliminary efficacy and elucidate the possible mechanism underlying the observed effects, is undertaken. Since there are limited effective treatment for AD, this procedure is potentially ground breaking if it proves to halt progression or even improve patients' cognition, function and behaviour. Indirectly, this will have enormous health economic benefit for Singapore and the developed world that is facing the silver tsunami. Findings from this pilot study will lay the groundwork for future trials and research collaboration in AD and other neurodegenerative diseases.
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
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of mild-moderate Alzheimer's disease (based on NIA-AA criteria);
- •Mini-Mental State Examination (MMSE) score 10-22;
- •Both participants and caregiver are able to understand English or Mandarin
- •Ability to provide informed consent or have a legally authorised representative to provide informed consent;
- •Good family support for post-treatment care and rehabilitation;
- •Fit for general anaesthesia/deep sedation and surgery (ASA 1-2; excluding the diagnosis of Alzheimer's Disease).
排除标准
- •Cognitive decline due to prior infection or autoimmune diseases;
- •History of major cerebrovascular events or significant cardiovascular diseases;
- •Inability to have the head turned passively by at least 40 degrees;
- •Previous neck lymph node surgery or irradiation;
- •Active infection or malignancy;
- •Any contraindications to surgery or lumbar puncture
- •Any contraindication to MRI/PET scan (eg. metallic implant that are not MRI-safe, known radiotracer allergy)
- •Experimental Alzheimer's Disease treatment within the past 6 months. • Current use of monoclonal antibodies treatment (eg. lecanemab/donanemab)
研究组 & 干预措施
Surgical Intervention
This is single-arm, open-label proof of concept study.
干预措施: Deep cervical lymph node to venous bypass (DCLNV-BP) (Procedure)
结局指标
主要结局
Safety: Number of treatment-related adverse events
时间窗: Over 2 years
Treatment related adverse events and postoperative side effects eg. anaesthetic complications, infection, seroma, nerve or vascular injuries, wound healing issues, death.
Mini Mental State Examination
时间窗: Over 2 years
Quick assessment of the cognitive domain. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 3; (3) PO day 7; (4) PO day 14; (5) PO 6 week; (6) PO 3 months; (7) PO 6 months; (8) PO 1 year; (9) PO 2 years.
Montreal Cognitive Assessment
时间窗: Over 2 years
Brief assessment of the cognitive domains, especially in mild cognitive impairment, for memory, visuospatial skills, executive function. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
Clinical Dementia Rating (CDR)
时间窗: Over 2 years
Assessment administered to the participant and caregiver to test various cognitive domains (ie. orientation, attention and working memory, memory, visuospatial, language, executive function) and activities of daily living. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
Neuropsychiatric Inventory (NPI)
时间窗: Over 2 years
A comprehensive assessment of neuropsychiatric symptoms in patients with dementia, specifically behavioral changes, and administered to the main caregiver over about 5 minutes. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
Geriatric Depression Scale-Short Form (GDS-SF)
时间窗: Over 2 years
This assessment will take 5-7 minutes and will be administered to the participant to measure depressive symptoms. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
Quality of Life - Alzheimer's Disease (QoL-AD)
时间窗: Over 2 years
This assessment will take 5-10 minutes and will be administered to the participant to measure Quality of Life measures in AD. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
Zarit Burden Score
时间窗: Over 2 years
This assessment will take take 5-10 minutes and will be administered to the main caregiver to ascertain changes in caregiver burden.. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
Basic and instrumental Activities of Daily Living
时间窗: Over 2 years
This evaluation checklist will take under 5 minutes to assess participant's function status. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
Basic Gait Assessment
时间窗: Over 2 years
Basic gait assessment will be performed including (A) Gait Speed, (B) Timed up and go test, (C) 5X sit to stand test. Assessment to be performed at: (1) Baseline; (2) Postoperative(PO) day 14; (3) PO 6 week; (4) PO 3 months; (5) PO 6 months; (6) PO 1 year; (7) PO 2 years.
次要结局
- Fluid biomarkers(Over 1 year)
- Magnetic Resonance Imaging (MRI) of the Brain(Over 1 year)
- Positron Emission Tomography (PET) of the brain(Over 3 months)
研究者
Vincent Tay Khwee Soon
Consultant Plastic Surgeon
Changi General Hospital