Deep Cervical LymphatIc-Venous Anastomosis for Alzheimer's Disease

March 24, 2026 updated by: Hui-Sheng Chen, General Hospital of Shenyang Military Region

Deep Cervical LymphatIc-Venous Anastomosis for Alzheimer's Disease (CLIVA-AD): a Prospective, Single-center, Randomized, Double Blinded Trial

Lymphaticovenous anastomosis (LVA) is a microsurgical technique that involves anastomosing fine lymphatic vessels with adjacent veins to reestablish lymphatic drainage pathways. It is used in the treatment of lymphedema-related conditions and is characterized by minimal invasiveness and rapid recovery. Based on findings from animal studies, some physicians in China have attempted deep cervical lymphatic-venous anastomosis to improve intracranial lymphatic drainage in patients with Alzheimer's disease (AD). Most studies, including those from our center, have observed early postoperative improvements in various domains such as mood, memory, executive function, and communication abilities in the majority of patients. However, these symptomatic improvements are not sustained. The reasons for the early improvements remain unclear. Are they due to enhanced lymphatic drainage resulting from the surgery itself, or are they attributable to other factors such as anesthetic effects, vascular release, or modulation of sympathetic nerves? Therefore, it is necessary to conduct a randomized controlled trial with a sham surgery group to clarify the causes of early clinical symptom improvements. Based on this, this project aims to carry out a prospective, single-center, randomized double-blind controlled study to evaluate whether the early symptomatic improvements following deep cervical LVA in AD patients are attributable to the surgical intervention itself or to other aspects of the procedure.

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.

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.
50

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 Locations

  • China
      • Shenyang, China, 110016
        • Recruiting
        • Department of Neurology, General Hospital of Northern Theater Command
        • 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:

  • Age 50-80 years (inclusive), regardless of gender.
  • Meeting the diagnostic criteria for Mild Cognitive Impairment or mild to moderate dementia due to Alzheimer's disease (according to the 2024 AA clinical diagnostic criteria for AD-related dementia).
  • Disease duration of 6 months or longer, with no clinical improvement after 3 months or more of conservative treatment.
  • MMSE score: 12-26.
  • Biomarker confirmation of AD: positive Aβ-PET and tau-PET, or positive cerebrospinal fluid biomarkers.
  • Having a reliable caregiver (providing companionship for ≥3 hours per day).
  • Signed written informed consent from the patient or legally authorized representative.

Exclusion Criteria:

  • Contraindications to MRI, ICG angiography, or PET.
  • Contraindications to surgery or anesthesia, such as coagulation disorders (platelet count <100×10⁹/L, INR >1.7).
  • Comorbid major organ dysfunction, such as reduced left ventricular ejection fraction, severe hepatic or renal insufficiency (AST or ALT >3 times the upper limit of normal; eGFR <30 mL/min/1.73m²).
  • Intracranial structural lesions indicated by MRI, including brain tumors, cerebral infarction, intracranial hemorrhage, aneurysms, arteriovenous malformations, hydrocephalus, etc.
  • MRI findings suggestive of significant cerebral small vessel disease features: more than one lacunar infarction in the deep white matter and periventricular regions and/or white matter hyperintensity (WMH) with a Fazekas grade >2, or the presence of ≥4 cerebral microbleeds.
  • Other causes of dementia, such as hypothyroidism or vitamin B12 deficiency.
  • Drug/alcohol addiction.
  • Severe psychiatric illness or suicide risk.
  • Comorbid medical conditions with a life expectancy of less than 1 year.
  • Participation in another interventional trial within the past 3 months.
  • Poor compliance or judged by the investigator as unsuitable for participation.
  • Patients receiving therapy with Lecanemab or Donanemab.
  • Other conditions that the researcher deems unsuitable for participation in this study.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

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: LVA group
patients will receive lymphaticovenous anastomosis
Procedure: deep cervical lymphaticovenous anastomosis
patients will receive deep cervical lymphaticovenous anastomosis
Sham Comparator: Sham group
patients will undergo the LVA surgical procedure without performing the lymphaticovenous anastomosis.
Procedure: deep cervical lymphaticovenous anastomosis
patients will receive deep cervical lymphaticovenous anastomosis

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
Changes in Montreal Cognitive Assessment (MoCA) score
Time Frame: 4±1 days
MoCA ranges from 0 to 30, with higher score meaning better outcome
4±1 days
Changes in Mini-mental State Examination (MMSE) score
Time Frame: 4±1 days
MMSE ranges from 0 to 30, with higher score meaning better outcome
4±1 days
Changes in Barthel index (BI)
Time Frame: 4±1 days
BI ranges from 0 to 100, with higher score meaning better outcome
4±1 days
Changes in Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus)
Time Frame: 4±1 days
CIBIC-plus ranges from 1 to 7, with higher score meaning worse outcome
4±1 days

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
Changes in Montreal Cognitive Assessment (MoCA) score
Time Frame: 90±7 days; 180±15 days; 270±20 days
MoCA ranges from 0 to 30, with higher score meaning better outcome
90±7 days; 180±15 days; 270±20 days
Changes in Mini-mental State Examination (MMSE) score
Time Frame: 90±7 days; 180±15 days; 270±20 days
MMSE ranges from 0 to 30, with higher score meaning better outcome
90±7 days; 180±15 days; 270±20 days
Changes in Barthel index (BI)
Time Frame: 90±7 days; 180±15 days; 270±20 days
BI ranges from 0 to 100, with higher score meaning better outcome
90±7 days; 180±15 days; 270±20 days
Changes in Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus)
Time Frame: 90±7 days; 180±15 days; 270±20 days
CIBIC-plus ranges from 1 to 7, with higher score meaning worse outcome
90±7 days; 180±15 days; 270±20 days
Severe adverse events
Time Frame: Perioperative period
Perioperative period

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.
General Hospital of Shenyang Military Region

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 (Actual)

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.
March 20, 2026

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.
August 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.
August 30, 2027

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).
December 8, 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.
December 8, 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.
December 19, 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, 2026

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 24, 2026

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.
March 1, 2026

More Information

Terms related to this study

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.
  • Y (2025) 250

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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