Deep Cervical LymphatIc-Venous Anastomosis for Alzheimer's Disease

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: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Procedure: deep cervical lymphaticovenous anastomosis

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shenyang, China, 110016
    • Recruiting
    • Department of Neurology, General Hospital of Northern Theater Command
    • Contact: Hui-Sheng Chen, Ph.D.; Phone Number: +86 13352452086; Email: chszh@aliyun.com

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Changes in Montreal Cognitive Assessment (MoCA) score	MoCA ranges from 0 to 30, with higher score meaning better outcome	4±1 days
Changes in Mini-mental State Examination (MMSE) score	MMSE ranges from 0 to 30, with higher score meaning better outcome	4±1 days
Changes in Barthel index (BI)	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)	CIBIC-plus ranges from 1 to 7, with higher score meaning worse outcome	4±1 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Montreal Cognitive Assessment (MoCA) score	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	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)	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)	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		Perioperative period

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID 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