Deep Cervical Lymphovenous Anastomosis for Severe Alzheimer's Disease

NCT07669272 | Not Yet Recruiting

• 2 other identifiers: KY2026120(A)KY2024136
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer s Disease

Keywords

Alzheimer Disease; Severe Dementia; Cognitive Impairment; Neurodegenerative Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Sum of Boxes (CDR-SB) Total Score

  Baseline (pre-operation), 1 month and 6 months after surgery

• Mini-Mental State Examination (MMSE) Score

  Baseline (pre-operation), 1 month, 6 months and 12 months after surgery

• Zarit Burden Interview (ZBI) Score

  Baseline (pre-operation), 1 month, 6 months and 12 months after surgery

• Amyloid-beta (Aβ) PET-CT Centiloid Value

  Baseline (pre-operation), 12 months after surgery

Study Arms (1)

Deep Cervical Lymphovenous Anastomosis plus Routine Treatment

EXPERIMENTAL

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; Other: Routine Treatment

Interventions

Routine Treatment OTHER

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.

Deep Cervical Lymphovenous Anastomosis plus Routine Treatment

Deep Cervical Lymphovenous Anastomosis PROCEDURE

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.

Deep Cervical Lymphovenous Anastomosis plus Routine Treatment

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Southwest Hospital, China: lead

Study Sites (1)

The First Affiliated Hospital of Army Medical University (Southwest Hospital)

Chongqing, Chongqing Municipality, 400038, China

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Cognitive Dysfunction; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Central Study Contacts

Rong Hu, MD

CONTACT

+8602368765911; huchrong@tmmu.edu.cn

Jingyu Chen, MD

CONTACT

+8602368765911; 283686484@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor

Study Record Dates

• First Submitted: June 21, 2026
• First Posted: June 25, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: June 25, 2026

Record last verified: 2026-06

Locations

CN (1)