Deep Cervical Lymphatic Venous Anastomosis in the Treatment of Alzheimer's Disease (CLEAN-AD)

NCT07073066 | Recruiting DMC

• 1 other identifier: KY2025-089-02
• Study Type: interventional
• Target: 376
• Locations: 1 country
• Sites: 9

Brief Summary

This multicenter, prospective, open-label, blinded-endpoint, randomized controlled trial is to evaluate the efficacy and safety of deep cervical lymphatic venous anastomosis (DC-LVA) plus usual care versus usual care in reduing the score of clinical dementia rating-sum of boxes (CDR-SB) at 12 months in patients with moderate-to-severe Alzheimer's Disease (AD).

Conditions

Alzheimers Disease

Keywords

Alzheimers disease; Cervical Lymphatic Venous Anastomosis; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• The change of Clinical Dementia Rating-Sum of Boxes score at 12th months after randomization

  The change of Clinical Dementia Rating-Sum of Boxes score (CDR-SB, 0-18 score, higher scores mean a worse outcome)

  From baseline to 12th months after randomization

Secondary Outcomes (15)

• The Change of Clinician's Interview-Based Impression of Change plus caregiver input score

  From baseline to 12th months after randomization

• The Change of Neuropsychiatric Inventory Score

  From baseline to 12th months after randomization

• The Change of Aβ PET-CT Centiloid value

  From baseline to 12th months after randomization

• The Change of Zarit Caregiver Interview of Alzheimer's Disease Score

  From baseline to 12th months after randomization

• The Change of Alzheimer's Disease Assessment Scale-Activity of Daily Living score

  From baseline to 12th months after randomization

Other Outcomes (10)

• The change of Clinical Dementia Rating-Sum of Boxes score during the open-label extension phase

  From baseline to 15th, 18th, 21th, and 24th months after randomization

• The Change of Clinician's Interview-Based Impression of Change plus caregiver input score during the open-label extension phase

  From baseline to 15th, 18th, 21th, and 24th months after randomization

• The Change of Neuropsychiatric Inventory Score during the open-label extension phase

  From baseline to 15th, 18th, 21th, and 24th months after randomization

Study Arms (2)

DC-LVA treatment plus usual care

EXPERIMENTAL

The intervention requires to perform bilateral deep cervical lymphatic venous anastomosis (DC-LVA). The usual care includes patients who were not using or were currently using medications for improving cognitive function.

Procedure: DC-LVA treatment plus usual care

Usual care

ACTIVE COMPARATOR

The usual care group includes patients who were not using or were currently using medications for improving cognitive function.

Other: Usual care

Interventions

DC-LVA treatment plus usual care PROCEDURE

Through cervical incision, the deep cervical lymphatic tissue is anatomically dissected and anastomosed with the venous system of the neck. Under indocyanine green (ICG) navigation, the flow of lymphatic fluid into the vein could be observed via ICG tracing fluorescence after surgery.

Also known as: LVA

DC-LVA treatment plus usual care

Usual care OTHER

The usual care group includes patients who were not using or were currently using medications for improving cognitive function.

Usual care

Eligibility Criteria

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

You may qualify if:

• Age 50-80 years, male or female.
• Diagnosed with AD according to NIA-AA criteria.
• Moderate-to-severe AD dementia, defined as Clinical Dementia Rating Scale Global Score (CDR-GS) ≥1.
• Mini-Mental State Examination (MMSE) score 10-20.
• The course of AD more than 6 months.
• If receiving an approved AD treatment, must be on a stable drug dose for at least 3 months prior to Baseline. AD Treatment-naïve subjects can be entered into the study.
• Have an identified caregiver (defined as a person able to support the subject for the duration of the study and who spends at least 8 hours per week with the subject). The caregiver must accompany with the participant at all study follow-up visits.
• Signed informed consent (from the participant or their relative, and the caregiver).

You may not qualify if:

• Any neurological condition other than AD that may affect cognitive function, including stroke, Parkinson's disease, epilepsy, intracranial tumors or space-occupying lesions, traumatic brain injury, intracranial infections, metabolic encephalopathy, etc.
• Other causes of dementia, including vascular dementia, hereditary cerebral small vessel disease, vitamin deficiency, or any other etiology leading to dementia.
• Previous evidence of severe stenosis (≥70%) in the middle cerebral artery and/or internal carotid artery.
• Presence of primary psychiatric disorders (such as schizophrenia, schizoaffective disorder, major depressive disorder, or bipolar disorder) rather than psychiatric symptoms caused by AD.
• Severe neurological deficits in limb movement, language, vision, hearing, or consciousness, or any condition that the investigator determines may prevent the completion of cognitive function assessments.
• History of drug or alcohol abuse or dependence.
• History of malignant tumors or prior radiotherapy or surgery involving the head and neck.
• Major surgical procedures or severe head or body trauma within the past 30 days.
• Presence of other life-threatening conditions with an expected survival time of less than 2 years.
• Contraindications to head MRI (including cardiac pacemakers/defibrillators, ferromagnetic metal implants, etc.).
• Severe diseases or functional impairment of the heart, lungs, liver, kidneys, or other solid organs, making the patient unable to tolerate anesthesia or DC-LVA.
• Severe bleeding tendency (including but not limited to): platelet count \<100×10⁹/L; heparin therapy within the last 48 hours with APTT ≥35 seconds; ongoing warfarin use with INR \>1.7.
• Requirement for long-term use of antithrombotic medications, with inability to discontinue them before surgery or potential risks associated with discontinuation.
• Uncontrolled persistent hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>95 mmHg).
• Co-infection with HIV or Treponema pallidum, or any uncontrolled infectious disease.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (9)

Dongguan Chashan Hospital

Dongguan, Guangdong, China

RECRUITING

Guangdong Second People's Hospital

Guangdong, Guangzhou, 510000, China

RECRUITING

Zhengzhou Central Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

First Affiliated Hospital of Shandong First Medical University

Jinan, Shandong, 250000, China

ACTIVE NOT RECRUITING

Shandong Provincial Public Health Clinical Center

Jinan, Shandong, 250000, China

RECRUITING

Shandong Provincial Third Hospital

Jinan, Shandong, 250000, China

RECRUITING

Jining First People's Hospital

Jining, Shandong, 272000, China

RECRUITING

The First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, 315000, China

RECRUITING

Beijing Tiantan Hopital, Capital Medical University

Beijing, 100070, China

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Yuesong Pan

CONTACT

0086-010-59975807; yuesongpan@aliyun.com

Yilong Wang

CONTACT

0086-010-67092222; yilong528@aliyun.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The intervention is performed by well-trained surgeons, and the endpoint assessment is evaluated blindly by well-trained neurologists.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This multicenter, prospective, open-label, blinded-endpoint, randomized controlled trial

Study Record Dates

• First Submitted: May 11, 2025
• First Posted: July 18, 2025
• Study Start: March 13, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2029
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)