Cervical Lymphatico-Venous Bypass for Treatment of Alzheimer's Disease - Proof of Concept Study (CLyVeB-AD-1 Study)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Deep cervical lymph node to venous bypass (DCLNV-BP).
- Who it may be relevant to
- Registry conditions: Alzheimer Disease, Dementia Alzheimer Type, Dementia Alzheimer's Type, Alzheimer's Disease. Basic parameters: 50 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Singapore
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Procedure Deep cervical lymph node to venous bypass (DCLNV-BP)
Participants will under bilateral deep cervical lymph node to venous bypass procedure under general anaesthesia.
Primary outcome measures
- Safety: Number of treatment-related adverse events [Time frame: Over 2 years]
- Mini Mental State Examination [Time frame: Over 2 years]
- Montreal Cognitive Assessment [Time frame: Over 2 years]
- Clinical Dementia Rating (CDR) [Time frame: Over 2 years]
- Neuropsychiatric Inventory (NPI) [Time frame: Over 2 years]
- Geriatric Depression Scale-Short Form (GDS-SF) [Time frame: Over 2 years]
- Quality of Life - Alzheimer's Disease (QoL-AD) [Time frame: Over 2 years]
- Zarit Burden Score [Time frame: Over 2 years]
- Basic and instrumental Activities of Daily Living [Time frame: Over 2 years]
- Basic Gait Assessment [Time frame: Over 2 years]
Secondary outcome measures (3)
- Fluid biomarkers [Time frame: Over 1 year]
- Magnetic Resonance Imaging (MRI) of the Brain [Time frame: Over 1 year]
- Positron Emission Tomography (PET) of the brain [Time frame: Over 3 months]
Eligibility criteria
Inclusion criteria
- 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).
Exclusion criteria
- 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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Singapore · 1 center
- Changi General Hospital — Singapore
Identifiers
NCT: NCT06965062 · ClyVeB-AD-1