An Exploratory Study to Confirm Efficacy of Modified Deep Cervical Lymphovenous Anastomosis (LVA) in Alzheimer's Disease/ Parkinson's Disease (SOLVEN)

March 6, 2025 updated by: Youmao Zheng, MM, Zhejiang Provincial People's Hospital

A Prospective, Single-center, Single-arm, Exploratory, 24-Month Study to Confirm Efficacy of Modified Deep Cervical Lymphovenous Anastomosis (LVA) in Subjects with Alzheimer's Disease/ Parkinson's Disease

Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by pathological protein accumulation in the brain-Aβ/tau in AD and α-synuclein in PD. Recent studies have indicated that age-related lymphatic vessel atrophy compromises the metabolic clearance capacity of meningeal lymphatic vessels, potentially disrupting the equilibrium between production and clearance of Aβ/α-synuclein, ultimately leading to pathological accumulation of these proteins within the brain. Deep cervical lymphovenous anastomosis (LVA), a surgical technique proven effective in restoring lymphatic drainage in lymphedema, may enhance clearance of neurotoxic proteins by improving cervical lymphatic outflow. This project aims to evaluate the efficacy of modified deep cervical LVA in treating AD and PD, establishing a novel therapeutic strategy to modify disease progression and improve quality of life in neurodegenerative disorders, additionally offering the pathogenic mechanisms underlying neurodegenerative disorders.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Alzheimer's disease (AD) and Parkinson's disease (PD) are progressive neurodegenerative disorders characterized by pathological protein aggregation-Aβ plaques and tau tangles in AD, and α-synuclein Lewy bodies in PD. Emerging evidence implicates that the glymphatic-meningeal lymphatic system and deep cervical lymph nodes constitute the central pathway for metabolite clearance of cerebral macromolecules. Aging-associated lymphatic vessel atrophy disrupts the equilibrium between protein production and clearance, exacerbating neurotoxicity. Deep cervical lymphovenous anastomosis (LVA), a surgical technique validated in lymphedema management, aims to restore cervical lymphatic drainage and enhance glymphatic-mediated protein clearance. This study investigates the therapeutic potential of modified deep cervical LVA in AD and PD. A prospective cohort will undergo modified deep cervical LVA with longitudinal assessments, including cerebrospinal fluid (CSF) and plasma biomarkers (Aβ42, p-tau181, p-tau217, GFAP, NfL, α-synuclein), neuroimaging (MRI and PET-CT), and clinical endpoints (CDR, MMSE, MoCA, BADL and IADL for AD, UPDRS and PDQ-39 for PD). Mechanistically, we hypothesize that modified deep cervical LVA will reduce intracranial pressure gradients, augment meningeal lymph flow, and accelerate interstitial waste drainage, thereby mitigating neuroinflammation and neuronal damage. This trial aims to verify the efficacy of modified deep cervical LVA to modify disease progression in AD and PD, providing a surgically scalable approach to delay progression of neurodegenerative disorders and improve patient quality of life.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
160

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310014
        • Recruiting
        • Zhejiang Provincial People's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Alzheimer's disease:

  1. Male or female, the age ranged from 50 to 75 years old
  2. Informed consent signed and dated by patient or legal representative
  3. Patients diagnosed principally with mild cognitive impairment or dementia caused by Alzheimer's disease
  4. Positive result of Amyloid PET imaging (Centiloids ≥37)
  5. HAMD score ≤17
  6. Hachinski score ≤4 Patients who meet ASA (American Society of Anesthesiologists) grade I-III criteria

Parkinson's disease:

  1. Male or female, the age ranged from 50 to 80 years old
  2. Informed consent signed and dated by patient or legal representative
  3. Patients diagnosed with Parkinson's disease or probable Parkinson's disease according to the Clinical Diagnostic Criteria for Parkinson's Disease in China (2016) or MDS
  4. Stage I-IV patients according to Hoehn and Yahr Scale
  5. Patients documented history of Parkinson's disease for more than 2-5 years to ensure clinical stability of symptoms and exclude the possibility of early misdiagnosis of other conditions

Exclusion Criteria:

  1. Contraindications for MRI, ICG angiography, or PET scanning
  2. Contraindications for lumbar puncture
  3. Functional impairment of vital organs (cardiac, pulmonary, renal, hepatic), including reduced left ventricular ejection fraction, prolonged QT interval, severe pulmonary diseases, and severe hepatic/renal insufficiency
  4. MRI results suggesting intracranial active/acute pathologies, including infections, space-occupying lesions, major hemorrhages, or ≥4 lobar microhemorrhages;
  5. Conditions predisposing to increased intracranial hemorrhage risk, such as hematological disorders, hemorrhagic/coagulation disorders;
  6. Poorly controlled thyroid dysfunction;
  7. Cerebrovascular or systemic vasculopathy;
  8. Severe cardiac disease or hemodynamic instability;
  9. Uncontrolled severe hypertension;
  10. Substance use disorders (including illicit drugs, anesthetics, and alcohol dependence);
  11. Active severe infections, including HIV positivity and acute critical infections;
  12. Severe psychiatric disorders or significant suicide risk;
  13. Chronic hypnotic use (more than twice weekly for over one month);
  14. History of untreated/uncured malignancies;
  15. Participation in other interventional clinical trials within preceding 3 months;
  16. Poor compliance with inability/unwillingness to complete scheduled postoperative follow-ups;
  17. Other investigator-determined contraindications for trial participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: The clinically diagnosed patients with MCI or mild-moderate dementia caused by AD/PD
Procedure: Modified deep cervical Lymphatic-Venous Anastomosis
Deep cervical lymph-vein anastomosis surgery, connecting deep cervical lymph input vein vessels to enhance glymphatic-mediated protein clearance

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Alzheimer's disease: Change in Clinical Dementia Rating Scale sum of the boxes (CDR-SB)
Time Frame: up to 2 years
The Clinical Dementia Rating Scale sum of the boxes (CDR-SB) will be used to evaluate the general cognitive function. CDR-SB ranges from 0 to 18, and higher value represents a worse outcome.
up to 2 years
Alzheimer's disease: Change in Mini-mental State Examination (MMSE)
Time Frame: up to 2 years
The Mini-mental State Examination (MMSE) will be used to evaluate the general cognitive function. MMSE ranges from 0 to 30, and higher value represents a better outcome.
up to 2 years
Alzheimer's disease: Change in Montreal Cognitive Assessment (MoCA)
Time Frame: up to 2 years
The Montreal Cognitive Assessment (MoCA) will be used to evaluate the general cognitive function. MoCA ranges from 0 to 30, and higher value represents a better outcome.
up to 2 years
Alzheimer's disease: Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Severe Version) (ADCS-ADL-SEV)
Time Frame: up to 2 years
The ADCS-ADL-SEV consists of 19 items. Ratings reflect caregiver observations about the patient's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 54, with lower values over time reflecting functional deterioration.
up to 2 years
Parkinson's disease：Change in Unified Parkinson's Disease Rating Scale (UPDRS)
Time Frame: up to 2 years
The scale assesses the functional status of patients with parksinon´s disease, including the independency of daily activities, mood, secondary effects of medications and motor complications. The total UPDRS score ranges from 0 to 199 points, with higher scores indicating more severe symptoms.
up to 2 years
Parkinson's disease：Change in The Hoehn and Yahr Scale
Time Frame: up to 2 years
The Hoehn and Yahr (H&Y) scale is the most widely used and universally accepted staging system for overall functional disability in Parkinson's disease. The H&Y Scale categorizes Parkinson's disease progression into 7 stages. Each stage reflects worsening motor function and loss of independence.
up to 2 years
Parkinson's disease：Change in Parkinson's Disease Questionnaire-39 (PDQ-39)
Time Frame: up to 2 years
The Parkinson's Disease Questionnaire-39 (PDQ-39) is a vital tool for assessing the quality of life in Parkinson's disease patients. The total score ranges from 0 to 100 points, with higher scores indicating worse quality of life.
up to 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Alzheimer's disease: Change in amyloid deposit in brain
Time Frame: baseline, 1year, 2 years
Change from baseline as measured by amyloid positron emission tomography (PET) scan using centiloids. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.
baseline, 1year, 2 years
Alzheimer's disease: Change in brain Tau deposition in a subset of participants
Time Frame: baseline, 1year, 2 years
Change from baseline as measured by Tau PET scan
baseline, 1year, 2 years
Alzheimer's disease: Change in fluid biomarker
Time Frame: up to 2 years
Change from baseline in cerebrospinal fluid (CSF)/plasma p-tau217, p-tau181, Aβ42, GFAP and NfL levels
up to 2 years
Alzheimer's disease: Change in Neuropsychiatric Inventory (NPI-Q) Total Severity Score
Time Frame: up to 2 years
The NPI-Q is a brief, caregiver-reported assessment of neuropsychiatric symptoms associated with dementia. The NPI-Q yields total scores for Severity and Distress, reflecting the sum of ratings across all domains, with higher scores indicating a greater degree of symptom severity and caregiver distress, respectively.
up to 2 years
Alzheimer's disease: Change in Clinical Global Impression
Time Frame: up to 2 years
The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) is used to assess the severity and progression of AD, where scores from 0 to 7 represent the spectrum of symptom intensity (0 = asymptomatic to 7 = extremely severe). The Efficacy Index (EI), a composite metric balancing therapeutic benefits and side effects, ultimately reflects the efficacy of surgical interventions for AD.
up to 2 years
Alzheimer's disease: Changes in the functional connectivity in brain in a subset of participants
Time Frame: baseline, 1year, 2 years
Change from baseline in disrupted functional connectivity as measured by functional MRI (fMRI)
baseline, 1year, 2 years
Parkinson's disease: Change in fluid biomarker
Time Frame: up to 2 years
Change from baseline in cerebrospinal fluid (CSF)/plasma α-synuclein, GFAP, NfL levels
up to 2 years
Changes in the hippocampal volume
Time Frame: baseline, 1year, 2 years
Change from baseline in hippocampal volume (mm3) as measured by structural Magnetic Resonance Imaging (sMRI)
baseline, 1year, 2 years
Changes in the cortical thickness
Time Frame: baseline, 1year, 2 years
Change from baseline in cortical thickness (mm) as measured by structural Magnetic Resonance Imaging (sMRI)
baseline, 1year, 2 years
Changes in the water diffusion characteristics in brain
Time Frame: baseline, 1year, 2 years
Change from baseline in water diffusion reflects the White Matter Hyperintensities (WMH)/efficiency of lymphatic drainage as measured by MRI
baseline, 1year, 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zhejiang Provincial People's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Zybio Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 28, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KY2025008

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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