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NCT Number: NCT07328386

Effect of Cervical Lymphaticovenous and Lymph Node-to-Vein Anastomosis in Patients With Intracranial Lymphatic Circulation Disorder

This study is a single-center, prospective clinical trial designed to evaluate the therapeutic effects of lymphaticovenular anastomosis (LVA) and lymph node-venous anastomosis (LNVA) in patients with intracranial lymphatic circulation disorders. Following voluntary written informed consent, screening assessments will be performed in accordance with the clinical trial protocol. Eligibility will be determined based on the predefined inclusion and exclusion criteria, and eligible subjects will be enrolled in the study. Enrolled participants will undergo cognitive function assessments at baseline (pre-surgery) and at 1, 3, 6, 9, 12, 18, and 24 months postoperatively for follow-up. Cognitive evaluations will not be additionally performed for research purposes but will be conducted in accordance with the existing clinical care schedule and standard treatment guidelines.

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Key information

Conditions

Intracranial Lymphatic Circulation Disorder Alzheimer Disease Alzheimer's Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

19 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

There are several theories regarding the causes of mild cognitive impairment (MCI) and dementia, and one of the commonly proposed mechanisms involves the accumulation of amyloid, a metabolic waste product, within the brain parenchyma. This accumulation is thought to result from impaired clearance of waste from the brain. Accordingly, impaired function of the brain's waste drainage system may contribute to the development of cognitive symptoms.

Because waste clearance from the brain occurs through lymphatic pathways, dysfunction of lymphatic circulation has been identified as an important contributing factor to MCI and dementia. However, due to the minute diameter of lymphatic vessels-typically less than 1 mm-direct therapeutic interventions targeting lymphatic function have long remained unexplored.

Recent advances in supermicrosurgical techniques have enabled procedures on lymphatic vessels as small as 0.2-0.3 mm, leading to the development of novel treatments for lymphatic circulation disorders. For example, patients with upper or lower extremity lymphedema, a representative condition of lymphatic dysfunction, have shown significant improvement following lymphaticovenular anastomosis (LVA) or lymph node-venous anastomosis (LNVA).

Lymphedema results from obstruction or damage to lymphatic pathways, causing the accumulation of lymphatic fluid in tissues. LVA and LNVA are microsurgical procedures that create new bypass routes by connecting lymphatic vessels or lymph nodes directly to adjacent veins, thereby allowing lymphatic fluid to drain into the venous system and re-enter systemic circulation. These procedures have been performed for more than two decades, with excellent therapeutic outcomes reported over the past five years. At Asan Medical Center, more than 100 such procedures are successfully performed annually.

Furthermore, based on the same principle applied in limb lymphedema, recent case-level studies have suggested that performing LVA or LNVA in lymphatic pathways or lymph nodes responsible for cerebral waste clearance may improve degenerative neurological conditions, including Alzheimer's disease. Based on this accumulated knowledge and surgical expertise, cervical lymphaticovenular anastomosis and cervical lymph node-venous anastomosis will be performed to connect lymphatic vessels and lymph nodes involved in cerebral lymphatic drainage to adjacent veins.

It is hypothesized that this procedure may help slow disease progression, preserve quality of life, and potentially improve cognitive function in patients with mild cognitive impairment or dementia.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients aged 19 years or older who are diagnosed with intracranial lymphatic circulation disorder based on neurological evaluation.
  • Global Deterioration Scale (GDS) score between 3 and 5 at screening.
  • Diagnosis of Alzheimer's disease confirmed by amyloid PET-CT or CSF amyloid testing, showing amyloid accumulation associated with lymphatic circulation disorder.
  • Able to provide written informed consent to participate in the study voluntarily.

Exclusion criteria

  • Unable to undergo follow-up evaluation for at least 12 months after surgery.
  • Diagnosed with vascular dementia.
  • Presence of structural brain disease other than intracranial lymphatic circulation disorder.
  • Known hypersensitivity to indocyanine green (ICG).
  • Uncontrolled systemic medical conditions such as severe cardiopulmonary, renal, hepatic, or endocrine disorders.
  • History of previous neck surgery.
  • Refusal to participate or failure to provide informed consent.
  • Determined by the principal investigator to be unsuitable for participation due to any other clinical reason.

Treatment and study plan

Cervical Lymphaticovenous and Lymph Node-to-Vein Anastomosis

Procedure

This microsurgical procedure involves connecting the cervical lymphatic vessels and lymph nodes to adjacent veins to enhance lymphatic drainage from the brain. The purpose of the surgery is to reduce amyloid accumulation and improve cognitive function in patients with intracranial lymphatic circulation disorders.

Before the operation, ultrasound imaging is used to identify the lymphatic vessels, lymph nodes, and nearby veins. A small incision of approximately 2-3 cm is made along the sternocleidomastoid muscle. Indocyanine green (ICG) dye is injected to visualize lymphatic flow, and under microscopic guidance, the lymphatic structures are anastomosed to the adjacent veins. Finally, the incision is closed with adhesive, and no postoperative drainage is required.

Primary outcomes

  1. Change in Global Deterioration Scale (GDS) Score

    Time frame: From preoperative baseline to postoperative Months 1, 3, 6, 9, 12, 18, and 24

    Cognitive decline will be assessed using the Global Deterioration Scale (GDS). The GDS score ranges from 1 to 7, with higher scores indicating more severe cognitive impairment. The outcome measure is the change in GDS score from baseline to postoperative follow-up visits. Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.

  2. Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score

    Time frame: Preoperative baseline and postoperative Month 12

    Dementia severity will be evaluated using the Clinical Dementia Rating - Sum of Boxes (CDR-SB).

    CDR-SB scores range from 0 to 18, with higher scores indicating more severe cognitive impairment The outcome measure is the change in CDR-SB score from baseline to postoperative follow-up visits.

    Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.

  3. Change in Korean Mini-Mental State Examination (K-MMSE) Score

    Time frame: From preoperative baseline to postoperative Months 1, 3, 6, 9, 12, 18, and 24

    Cognitive function will be assessed using the Korean Mini-Mental State Examination (K-MMSE).

    K-MMSE scores range from 0 to 30, with higher scores indicating better cognitive function.

    The outcome measure is the change in K-MMSE scores from the preoperative baseline to 12 months after surgery.

    Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.

  4. Change in Montreal Cognitive Assessment (MoCA) Score

    Time frame: Preoperative baseline; postoperative Day 4; Months 1, 3, 6, 9, 12, 18, and 24

    Cognitive performance will be assessed using the Montreal Cognitive Assessment (MoCA).

    MoCA scores range from 0 to 30, with higher scores indicating better cognitive performance.

    The outcome measure is the change in MoCA scores from the preoperative baseline to 12 months after surgery.

    Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.

  5. Change in Seoul Neuropsychological Screening Battery (SNSB) Score

    Time frame: Preoperative baseline; postoperative Months 6, 12, and 24

    Cognitive function will be assessed using the Seoul Neuropsychological Screening Battery (SNSB), a comprehensive neuropsychological test battery evaluating multiple cognitive domains including attention, language, visuospatial function, memory, and executive function.

    SNSB provides domain-specific and composite scores, with higher scores generally indicating better cognitive performance, depending on the specific subtest.

    Score ranges differ across subtests within the SNSB. The outcome measure is the change in SNSB scores from the preoperative baseline to postoperative follow-up assessments.

    Scores will be compared between the surgical (LVA + LNVA) group and the medication-only control group.

Secondary outcomes

  1. Incidence of Surgical Complications and Adverse Events

    Time frame: From the day of surgery through postoperative Month 24

    Surgical complications and adverse events will be monitored throughout the study period to evaluate the safety of cervical lymphaticovenous and lymph node-to-vein anastomosis.

    Complications may include postoperative infection, wound issues, bleeding, lymphatic leakage, anesthetic complications, or other procedure-related adverse events.

    Adverse events will be recorded according to clinical severity and temporal relationship to the intervention.

    The outcome measure is the incidence and type of complications occurring during the follow-up period.

  2. Change in Amyloid-Related Blood Biomarkers

    Time frame: Preoperative baseline; postoperative Months 1, 3, 6, 12, and 24

    The outcome measure is the change from the preoperative baseline to postoperative follow-up assessments in pre-specified amyloid-related blood biomarkers (e.g., amyloid-beta-related markers). Changes in amyloid-related blood biomarkers will be compared between the surgical (LVA + LNVA) group and the medication-only control group.

  3. Change in Blood Biomarkers of Neurodegeneration

    Time frame: Preoperative baseline; postoperative Months 1, 3, 6, 12, and 24

    The outcome measure is the change from the preoperative baseline to postoperative follow-up assessments in pre-specified blood biomarkers of neurodegeneration (e.g., phosphorylated tau). Changes in neurodegeneration-related blood biomarkers will be compared between the surgical (LVA + LNVA) group and the medication-only control group.

Other outcomes

  1. Change in Gait Function Test Performance

    Time frame: Screening; postoperative Months 1, 3, 6, 9, 12, 18, and 24

    The outcome measure is the change in gait function from the screening assessment to postoperative follow-up assessments, as measured by a standardized gait function test yielding a single composite score according to the study protocol.

  2. Change in Amyloid PET Imaging Findings

    Time frame: Screening; postoperative Month 6

    Amyloid positron emission tomography (PET) imaging will be performed to observe any changes in amyloid-related findings before and after the surgical intervention.

    PET imaging is conducted at screening to confirm eligibility and again at postoperative Month 6 to evaluate interval changes.

    Any differences in overall PET imaging appearance between the two time points will be examined and compared between the surgical (LVA + LNVA) group and the medication-only control group.

Study contacts

Contact information is provided by the study sponsor or research team.

Jin geon Guen, MD, PhD

CONTACT

[email protected]

+82230103600

Sponsors and collaborators

Lead sponsor

Hong Joonpio

Other

Registry information

Official study title

Effect of Cervical Lymphaticovenous Anastomosis and Cervical Lymph Node to Vein Anastomosis for the Patient With Intracranial Lymphatic Circulation Disorder

Acronym: CLVA-CLNA-ICLC

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jan 9, 2026
Registry last updated
Jan 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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