Efficacy of Lymphatic-Venous Anastomosis Plus Donepezil Versus Donepezil Alone for Alzheimer's Disease

NCT07680660 | Not Yet Recruiting DMC

• 1 other identifier: SH9H-2025-T549
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

This study employed a multicenter, randomized controlled trial (RCT) design to evaluate the efficacy and safety of deep cervical lymphatic/lymph node-venous anastomosis combined with oral donepezil compared to donepezil monotherapy in patients with Alzheimer's disease and moderate dementia. Participants were randomized using a central randomization system with stratified block design, with the study center and age group (50-64 years, 65-80 years) as stratification factors. While study participants and surgical investigators could not be blinded due to the nature of the intervention, efficacy assessors and imaging specialists remained blinded to ensure the objectivity and reliability of the findings. The intervention group received deep cervical lymphatic/lymph node-venous anastomosis (detailed surgical procedure is specified in the protocol) in combination with oral donepezil (5-10 mg/day), while the control group received oral donepezil alone. The total treatment and follow-up period was 18 months, with assessments conducted at baseline, 1 week, 1, 3, 6, 12, and 18 months post-operation. These included neuropsychological evaluations (MMSE, MoCA, CDR, BADL, IADL, NPI, AES), neuroimaging (MRI, PET, ultrasound), fluid biomarker analyses (CSF and blood levels of Aβ, Tau, neuroinflammatory factors, etc.), and safety monitoring. The primary efficacy endpoint was the change in CDR-SB score at 12 months post-treatment. Secondary endpoints included changes in multiple cognitive scales, neuroimaging metrics, and biomarkers at 18 months. Safety indicators encompassed adverse event recording, vital signs, and laboratory tests.

Conditions

Alzheimer s Disease

Keywords

cervical lymph vessel/node-venous anastomosis; LVA; Alzheimer

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score at Month 12

  The Clinical Dementia Rating-Sum of Boxes is a clinician-rated measure of dementia severity. The score ranges from 0 to 18, with higher scores indicating greater impairment and more severe dementia. The outcome measure is the change from baseline to Month 12. The scale will be administered face to face by trained evaluators blinded to treatment assignment, and results will be reviewed by an independent endpoint adjudication committee.

  Baseline and Month 12

Secondary Outcomes (70)

• Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score at Month 18

  Baseline and Month 18

• Change From Baseline in Mini-Mental State Examination Score at Month 18

  Baseline and Month 18

• Change From Baseline in Montreal Cognitive Assessment Score at Month 18

  Baseline and Month 18

• Change From Baseline in 18-item Apathy Evaluation Scale Score at Month 18

  Baseline and Month 18

• Change From Baseline in Neuropsychiatric Inventory Total Score at Month 18

  Baseline and Month 18

Study Arms (2)

Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group

EXPERIMENTAL

Procedure: Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil; Drug: Oral treatment with donepezil

Oral donepezil group

ACTIVE COMPARATOR

Drug: Oral treatment with donepezil

Interventions

Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil PROCEDURE

Under total intravenous anesthesia, the patient is placed supine with the head turned and shoulders elevated. A transverse neck incision is made, the platysma is opened, and the external jugular vein and great auricular nerve are exposed and protected. Dissection proceeds along the sternocleidomastoid muscle and carotid sheath to create two lymphatic composite flaps: a lateral IIB/III flap rich in deep cervical lymph nodes and lymphatic vessels, and a medial IIA flap containing the angular lymph node. Both flaps are prepared to ensure continuous lymphatic fluid outflow. Revascularization is then performed by end-to-end anastomosis of the IIA flap to a branch of the common facial vein or external jugular vein, and end-to-side anastomosis of the IIB/III flap to the internal or external jugular vein. After the anastomosis is completed, the incision is sutured layer by layer for cosmetic purposes.

Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group

Oral treatment with donepezil DRUG

After randomly assigned into the group, the study participants were given donepezil orally (the cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group began to take donepezil orally on the first day after operation, and the oral donepezil group began to take donepezil after completing the baseline examination), once a day, before sleep, starting at 5 mg/day, and adjusted to 10 mg/day after 6 weeks; if not tolerated, it will be maintained at 5 mg/day, continued for 6 weeks, and then 10 mg/day will be attempted again, with continuous administration for 18 months. If research participants still cannot tolerate the high dose, they may be maintained at 5 mg/day for 18 months.

Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group; Oral donepezil group

Eligibility Criteria

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

You may qualify if:

• The patient or guardian signs the informed consent form;
• Age 50-80 years (≥50 years, ≤80 years), male or female;
• The first diagnosis is Alzheimer's disease with dementia;
• MMSE score ≤24;
• Positive β-amyloid protein PET imaging findings;
• HAMD score ≤17;
• Hachinski score ≤7;
• No AD-related drug treatment has been received within the past 1 month;
• ASA grade 1-3 (≥ grade 1, ≤ grade 3);
• CDR-SB score of 9.5-15.5.

You may not qualify if:

• Presence of contraindications to MRI, ICG angiography, or PET scan;
• Presence of contraindications to lumbar puncture;
• Severe heart disease or unstable hemodynamic status;
• Severe lung disease, including severe obstructive, restrictive, or mixed ventilatory dysfunction, or acute inflammation within 3 months;
• Hepatic insufficiency, AST or ALT \>3 times the upper limit of normal;
• Renal insufficiency, GFR \<60 mL/min or need for blood purification treatment;
• MRI indicates active or acute intracranial lesions, including intracranial infection, space-occupying lesions, major hemorrhage, and ≥4 lobar microbleeds, etc.;
• History of cerebral hemorrhage or cerebral infarction with severe residual neurological dysfunction;
• Blood diseases, bleeding/coagulation disorders, coagulation dysfunction;
• Abnormal thyroid function;
• Moderate or severe stenosis of intracranial or cervical vessels with severe residual neurological dysfunction;
• Severe hypertension not effectively controlled, systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg;
• The disease requires systemic use of steroids;
• Drug addiction (including alcohol, narcotics, and alcohol dependence);
• Severe infectious diseases, including HIV positivity, severe infection, etc.;

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Study Sites (1)

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Shanghai, Huangpu, 200011, China

Location

Related Publications (17)

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MeSH Terms

Interventions

Donepezil; Therapeutics

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Central Study Contacts

Yixin Zhang

CONTACT

+86 13061775858; zhangyixin6688@163.com

Ke Li

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2026
• First Posted: July 2, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: July 22, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)