Alzheimer DiseaseCLyVeB-AD-1NCT06965062
Cervical Lymphatico-Venous Bypass for Treatment of Alzheimer's Disease - Proof of Concept Study (CLyVeB-AD-1 Study)
A study testing Deep cervical lymph node to venous bypass (DCLNV-BP) in people with Alzheimer Disease and Dementia Alzheimer Type, run by Vincent Tay Khwee Soon at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Alzheimer Disease, Dementia Alzheimer Type, Dementia Alzheimer's Type
- What is being tested?
- Deep cervical lymph node to venous bypass (DCLNV-BP)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Apr 2025to 31 Mar 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
Changi General Hospital
Singapore
Vincent K S Tay, BSc(Hons), MD, MRCS, MMed, MCI, vincent.tay.k.s@singhealth.com.sg
About this study
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)
- Being tested
- Deep cervical lymph node to venous bypass (DCLNV-BP)
- Keywords
- Alzheimer's Disease, Dementia, lymphatic surgery, lymphaticovenous anastomosis, lymphaticovenous bypass, cervical lymph node, meningeal lymphatic system, glymphatic system
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep cervical lymph node to venous bypass (DCLNV-BP)Procedure or surgery
Also called Lymphaticovenous anastomosis
Participants will under bilateral deep cervical lymph node to venous bypass procedure under general anaesthesia.
| Study group | Role | What they receive |
|---|---|---|
| Surgical Intervention | Experimental | This is single-arm, open-label proof of concept study. Receives: Procedure: Deep cervical lymph node to venous bypass (DCLNV-BP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Number of treatment-related adverse events
Treatment related adverse events and postoperative side effects eg. anaesthetic complications, infection, seroma, nerve or vascular injuries, wound healing issues, death.
Measured: Over 2 years
Mini Mental State Examination
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.
Measured: Over 2 years
Montreal Cognitive Assessment
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.
Measured: Over 2 years
Clinical Dementia Rating (CDR)
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.
Measured: Over 2 years
Neuropsychiatric Inventory (NPI)
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.
Measured: Over 2 years
Geriatric Depression Scale-Short Form (GDS-SF)
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.
Measured: Over 2 years
Quality of Life - Alzheimer's Disease (QoL-AD)
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.
Measured: Over 2 years
Zarit Burden Score
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.
Measured: Over 2 years
Basic and instrumental Activities of Daily Living
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.
Measured: Over 2 years
Basic Gait Assessment
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.
Measured: Over 2 years
Secondary outcomes (3)
Fluid biomarkers
Blood plasma and cerebrospinal fluids will be analysed for biomarkers related to Alzheimer's disease, neurodegeneration and lymphatic dysfunction. Blood plasma will be sampled at (1) Operative day; (2) Postoperative(PO) day 3; (3) PO day 7; (4) PO day 14; (5) PO 6 weeks; (6) PO 3 months; (7) PO 6 months; (8) PO 1 year. CSF will be sampled at (1) Operative day; (2) PO day 7; (3) PO 6 weeks [Optional]; (4) PO 3 months [Optional].
Measured: Over 1 year
Magnetic Resonance Imaging (MRI) of the Brain
Participants will undergo pre- and post-intervention MRI of the brain for evaluation of neuroanatomical pathology and surrogate markers of glymphatic function (eg. DTI-ALPS). The scans will be performed at (1) Baseline, (2) Postoperative Day 7, (3) Postoperative 3 months.
Measured: Over 1 year
Positron Emission Tomography (PET) of the brain
Participants will undergo pre- and post-intervention PET fluorodeoxyglucose (FDG) brain scan to provide functional spatial information on changes before and after the surgery (at 3 months).
Measured: Over 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2025
- Study start1 Apr 2025
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vincent Tay Khwee Soon
- Sponsor type
- University, hospital or other
- Collaborators
- Changi General Hospital, Singapore General Hospital, National Neuroscience Institute
- Responsible party
- Sponsor-investigator, Vincent Tay Khwee Soon, Changi General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06965062
- Sponsor's protocol ID
- ClyVeB-AD-1
- Acronym
- CLyVeB-AD-1
- Status last verified
- May 2025
- First submitted
- 17 Jan 2025
- Last updated
- 13 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fu X, Zhang J, Xiao Q, Li T, Li Q, Zhang S, Zeng W, Gong M, Cai P, Deng Z, Zhang X, Xin Y, Su L, Tian X, Wu K, Xiong L. Deep cervical lymphatic-venous anastomosis attenuates cognitive dysfunction and biomarker abnormalities in severe Alzheimer's disease: A prospective single-arm study. Alzheimers Dement. 2026 Feb;22(2):e71150. doi: 10.1002/alz.71150.
PubMed 41630624
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cervical Lymphatico-Venous Bypass for Treatment of Alzheimer's Disease - Proof of Concept Study (CLyVeB-AD-1 Study)
- ClinicalTrials.gov ID
- NCT06965062
- Acronym / sponsor ID
- CLyVeB-AD-1 / ClyVeB-AD-1
- Conditions
- Alzheimer Disease, Dementia Alzheimer Type, Dementia Alzheimer's Type, Alzheimer's Disease, Alzheimer's Disease (AD)
- Keywords
- Alzheimer's Disease, Dementia, lymphatic surgery, lymphaticovenous anastomosis, lymphaticovenous bypass, cervical lymph node, meningeal lymphatic system, glymphatic system
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Vincent Tay Khwee SoonUniversity, hospital or other
- Collaborators
- Changi General Hospital, Singapore General Hospital, National Neuroscience Institute
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 11 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Surgical Intervention | Experimental | Procedure: Deep cervical lymph node to venous bypass (DCLNV-BP)This is single-arm, open-label proof of concept study. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deep cervical lymph node to venous bypass (DCLNV-BP)Also: Lymphaticovenous anastomosisParticipants will under bilateral deep cervical lymph node to venous bypass procedure under general anaesthesia. | Procedure or surgery | Surgical Intervention |
Primary outcome
Safety: Number of treatment-related adverse events
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Derived from this study: PubMed 41630624Fu X, Zhang J, Xiao Q, Li T, Li Q, Zhang S, Zeng W, Gong M, Cai P, Deng Z, Zhang X, Xin Y, Su L, Tian X, Wu K, Xiong L. Deep cervical lymphatic-venous anastomosis attenuates cognitive dysfunction and biomarker abnormalities in severe Alzheimer's disease: A prospective single-arm study. Alzheimers Dement. 2026 Feb;22(2):e71150. doi: 10.1002/alz.71150.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deep cervical lymph node to venous bypass (DCLNV-BP) in people with Alzheimer Disease and Dementia Alzheimer Type, run by Vincent Tay Khwee Soon at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vincent KS Tay, MD, FAMS (+65 6788 8833, vincent.tay.k.s@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Number of treatment-related adverse events (time frame: Over 2 years). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06965062, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.