Deep Cervical Lymphovenous Anastomosis for Severe Alzheimer's Disease (DCLVA-AD)

A Single-arm, Prospective, Self-controlled Study on Efficacy and Safety of Deep Cervical Lymphovenous Anastomosis for Neurological Function in Patients With Severe Alzheimer's Disease

Alzheimer's disease (AD) is a severe neurodegenerative disease with heavy social burden. Current drugs cannot reverse disease progression. Brain glymphatic system and meningeal lymphatic dysfunction lead to impaired clearance of Aβ and Tau protein, which is an important pathogenesis of AD. Deep cervical lymphovenous anastomosis (DCLVA) can improve intracranial lymphatic drainage, promote the clearance of toxic proteins, and improve neurological function. This is a single-arm, prospective, self-controlled study to enroll 59 patients with severe AD (MMSE < 10). All patients receive bilateral DCLVA plus routine medication. The primary endpoint is change of CDR-SB score at 12 months post-operation. Secondary endpoints include MMSE, ZBI scores and Aβ PET-CT Centiloid value. This study aims to verify the efficacy and safety of DCLVA for severe AD.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer s Disease
• Intervention / Treatment: Procedure: Deep Cervical Lymphovenous Anastomosis; Other: Routine Treatment

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rong Hu, MD; Phone Number: +8602368765911; Email: huchrong@tmmu.edu.cn
• Study Contact Backup: Name: Jingyu Chen, MD; Phone Number: +8602368765911; Email: 283686484@qq.com

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400038
      • The First Affiliated Hospital of Army Medical University (Southwest Hospital)
      • Contact: Jingyu Chen, MD; Phone Number: +8602368765911; Email: 283686484@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meet the 2011 NIA-AA clinical diagnostic criteria for probable Alzheimer's disease dementia and the 2018 NIA-AA research framework biomarker criteria for AD.
• Aged 50 to 80 years (inclusive) at the time of signing informed consent.
• Severe cognitive dysfunction: Mini-Mental State Examination (MMSE) score < 10 points.
• Progressive cognitive deterioration for more than 6 months reported by patient or caregiver.
• No clinical improvement after more than 6 months of standardized drug treatment.
• Have a designated study companion who signs informed consent, contacts the patient at least 10 hours per week and accompanies study visits.
• Able to complete scale assessments and examinations independently or with companion assistance.
• Voluntarily comply with study procedures, examinations and surgical treatment.
• Patient or legal representative can sign written informed consent and abide by trial requirements.
• Patients and families are informed of study purpose, expected efficacy and potential risks, and voluntarily provide biological samples and participate in the study.

Exclusion Criteria:

• Severe central nervous system diseases (other than AD) that affect cognitive function or study compliance.
• Severe/unstable systemic diseases (cardiovascular, hepatic, renal, respiratory, endocrine, hematological, psychiatric diseases); life expectancy less than 24 months.
• Surgical contraindications: severe coagulation disorders, severe -cardiopulmonary diseases (myocardial infarction/respiratory failure within recent 30 days); severe liver damage (ALT/AST > 3 times upper limit of normal); severe renal insufficiency (eGFR < 30ml/min).
• Severe primary mental disorders (other than AD) that interfere with efficacy evaluation and cognitive assessment.
• History of intracranial hemorrhage or craniocerebral trauma within recent 1 year.
• Alcohol or drug abuse/dependence within recent 1 year.
• Allergy to indocyanine green, gadolinium contrast agent, 18F-florbetapir or 18F-flortaucipir.
• Contraindications for PET examination.
• Other conditions judged by investigators unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Deep Cervical Lymphovenous Anastomosis plus Routine Treatment; All participants receive one-time bilateral deep cervical lymphovenous anastomosis under microsurgery with indocyanine green lymphatic tracing. Conventional anti-Alzheimer's drugs are maintained throughout the study. All outcomes are compared with pre-operation baseline.

Procedure: Deep Cervical Lymphovenous Anastomosis; A one-time microsurgical procedure performed under general anesthesia. Indocyanine green (ICG) is injected for intraoperative lymphatic vessel tracing under a fluorescent surgical microscope. Lymphatic vessels or lymphatic flaps are anastomosed to cervical veins via end-to-side or end-to-end technique to improve intracranial lymphatic drainage. No additional surgical interventions are applied.; Other: Routine Treatment; Stable administration of standard drugs for Alzheimer's disease, including cholinesterase inhibitors and/or NMDA receptor antagonists, following clinical guidelines. Participants continue their original medication regimen throughout the whole study period without dose adjustment or drug switching.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Boxes (CDR-SB) Total Score	The CDR-SB total score ranges from 0 to 18 points. Higher scores indicate more severe cognitive impairment and functional decline. This outcome evaluates the change of total CDR-SB score in patients with severe Alzheimer's disease after receiving deep cervical lymphovenous anastomosis, to assess the therapeutic effect on neurological function.	Baseline (pre-operation), 12 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Boxes (CDR-SB) Total Score	The CDR-SB total score ranges from 0 to 18 points. Higher scores indicate more severe cognitive impairment and functional decline. This outcome evaluates the change of total CDR-SB score in patients with severe Alzheimer's disease after receiving deep cervical lymphovenous anastomosis, to assess the therapeutic effect on neurological function.	Baseline (pre-operation), 1 month and 6 months after surgery
Mini-Mental State Examination (MMSE) Score	MMSE total score ranges from 0 to 30. Higher scores represent better cognitive function. A score below 10 indicates severe cognitive impairment. This measure assesses changes in overall cognitive status after surgical intervention.	Baseline (pre-operation), 1 month, 6 months and 12 months after surgery
Zarit Burden Interview (ZBI) Score	ZBI total score ranges from 0 to 88. Higher scores mean heavier caregiver burden. It is used to evaluate the impact of treatment on the psychological and life burden of patients' caregivers.	Baseline (pre-operation), 1 month, 6 months and 12 months after surgery
Amyloid-beta (Aβ) PET-CT Centiloid Value	Centiloid value reflects the level of cerebral amyloid-beta deposition. Detect and compare the difference of brain Aβ deposition between baseline and 12 months post-operation.	Baseline (pre-operation), 12 months after surgery

Collaborators and Investigators

• Sponsor: Southwest Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: June 21, 2026
• First Submitted That Met QC Criteria: June 21, 2026
• First Posted (Actual): June 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 21, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Neurodegenerative Disease; Cognitive Impairment; Alzheimer Disease; Severe Dementia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Cognitive Dysfunction; Alzheimer Disease; Dementia; Neurodegenerative Diseases
• Other Study ID Numbers: KY2026120; (A)KY2024136 (Other Identifier: Ethics Committee of the First Affiliated Hospital of the Army Medical University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data (IPD) will not be shared externally. All participant data is stored and managed locally in compliance with Chinese medical data privacy regulations and hospital internal management rules.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No