Cervical Lymphatico-Venous Bypass for Treatment of Alzheimer's Disease - Proof of Concept Study (CLyVeB-AD-1 Study)

NCT ID: NCT06965062

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2030-03-31

Brief Summary

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.

Conditions

Alzheimer Disease; Dementia Alzheimer Type; Dementia Alzheimer's Type; Alzheimer's Disease; Alzheimer's Disease (AD)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Surgical Intervention

This is single-arm, open-label proof of concept study.

Group Type: EXPERIMENTAL

Deep cervical lymph node to venous bypass (DCLNV-BP)

Intervention Type: PROCEDURE

Participants will under bilateral deep cervical lymph node to venous bypass procedure under general anaesthesia.

Interventions

Deep cervical lymph node to venous bypass (DCLNV-BP)

Participants will under bilateral deep cervical lymph node to venous bypass procedure under general anaesthesia.

Intervention Type: PROCEDURE

Other Intervention Names

Lymphaticovenous anastomosis

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)

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Changi General Hospital

OTHER

Sponsor Role: collaborator

Singapore General Hospital

OTHER

Sponsor Role: collaborator

National Neuroscience Institute

OTHER

Sponsor Role: collaborator

Vincent Tay Khwee Soon

OTHER

Sponsor Role: lead

Responsible Party

Vincent Tay Khwee Soon

Consultant Plastic Surgeon

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Changi General Hospital

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Vincent KS Tay, MD, FAMS

Role: CONTACT

vincent.tay.k.s@singhealth.com.sg

+65 6788 8833

Jeremy MF Sun, MBBS, FAMS

Role: CONTACT

jeremy.sun.m.f@singhealth.com.sg

+65 90304976

Facility Contacts

Vincent K S Tay, BSc(Hons), MD, MRCS, MMed, MCI

Role: primary

vincent.tay.k.s@singhealth.com.sg

Other Identifiers

ClyVeB-AD-1

Identifier Type: -

Identifier Source: org_study_id