Deep cervical lymphatic‑venous anastomosis for treating Alzheimer's disease

Deep Cervical Lymphatic Venous Anastomosis in the Treatment of Alzheimer's Disease: A Multicenter, Prospective, Open-label, Blinded-Endpoint, Randomized Controlled Trial (CLEAN-AD)

This test tries a surgical connection called deep cervical lymphatic‑venous anastomosis plus usual care to see if it slows cognitive decline over 12 months in people aged 50–80 with moderate‑to‑severe Alzheimer's disease.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 376 (estimated)
• Ages: 50 Years to 80 Years
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Locations: 9 sites (Dongguan, Guangdong and 8 other locations)
• Trial ID: NCT07073066 on ClinicalTrials.gov

What this trial studies

This is a multicenter, prospective, open‑label, blinded‑endpoint, randomized controlled trial enrolling 754 people with moderate‑to‑severe Alzheimer's disease across centers in China. Participants are randomly assigned to receive deep cervical lymphatic‑venous anastomosis (DC‑LVA) plus usual care or usual care alone, with clinical assessments and biomarker imaging at baseline and follow‑up. The primary outcome is change in the Clinical Dementia Rating Sum of Boxes (CDR‑SB) at 12 months, and secondary outcomes include amyloid PET measures and safety endpoints. The trial targets patients with CDR global score ≥1 and MMSE 10–20, and requires an identified caregiver to accompany follow‑up visits.

Who should consider this trial

Good fit: Ideal candidates are people aged 50–80 with AD diagnosed by NIA‑AA criteria who have moderate‑to‑severe dementia (CDR‑GS ≥1, MMSE 10–20), have had symptoms >6 months, are stable on AD medications (or treatment‑naïve), and have an identified caregiver able to attend visits.

Not a fit: Patients are unlikely to benefit if they have other neurological conditions that affect cognition, major surgical contraindications, are outside the 50–80 age range, have very mild disease, or cannot provide informed consent and caregiver support.

Why it matters

Potential benefit: If successful, the procedure could slow clinical decline and lower brain amyloid signals in people with moderate‑to‑severe Alzheimer's disease, offering a new therapeutic option where few exist.

How similar studies have performed: Small case series have suggested possible benefit from DC‑LVA, but there are no prior randomized controlled trials testing this approach.

Eligibility criteria

Inclusion Criteria:

1. Age 50-80 years, male or female.
2. Diagnosed with AD according to NIA-AA criteria.
3. Moderate-to-severe AD dementia, defined as Clinical Dementia Rating Scale Global Score (CDR-GS) ≥1.
4. Mini-Mental State Examination (MMSE) score 10-20.
5. The course of AD more than 6 months.
6. 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.
7. 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.
8. Signed informed consent (from the participant or their relative, and the caregiver).

Exclusion Criteria:

1. 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.
2. Other causes of dementia, including vascular dementia, hereditary cerebral small vessel disease, vitamin deficiency, or any other etiology leading to dementia.
3. Previous evidence of severe stenosis (≥70%) in the middle cerebral artery and/or internal carotid artery.
4. Presence of primary psychiatric disorders (such as schizophrenia, schizoaffective disorder, major depressive disorder, or bipolar disorder) rather than psychiatric symptoms caused by AD.
5. 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.
6. History of drug or alcohol abuse or dependence.
7. History of malignant tumors or prior radiotherapy or surgery involving the head and neck.
8. Major surgical procedures or severe head or body trauma within the past 30 days.
9. Presence of other life-threatening conditions with an expected survival time of less than 2 years.
10. Contraindications to head MRI (including cardiac pacemakers/defibrillators, ferromagnetic metal implants, etc.).
11. 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.
12. 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.
13. Requirement for long-term use of antithrombotic medications, with inability to discontinue them before surgery or potential risks associated with discontinuation.
14. Uncontrolled persistent hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>95 mmHg).
15. Co-infection with HIV or Treponema pallidum, or any uncontrolled infectious disease.
16. Use of other investigational drugs or devices within 30 days prior to obtaining informed consent, or current participation in other interventional clinical studies.
17. Pregnancy, lactation, potential for pregnancy, or plans for pregnancy during the study period.
18. Immediate family members of the investigator (spouse, parents, children, or siblings), staff of the research institution or third-party organizations, or any other individuals with potential conflicts of interest related to the study.

Where this trial is running

Dongguan, Guangdong and 8 other locations

• Dongguan Chashan Hospital — Dongguan, Guangdong, China (Recruiting)
• Guangdong Second People's Hospital — Guangdong, Guangzhou, China (Recruiting)
• Zhengzhou Central Hospital — Zhengzhou, Henan, China (Recruiting)
• First Affiliated Hospital of Shandong First Medical University — Jinan, Shandong, China (Active_not_recruiting)
• Shandong Provincial Public Health Clinical Center — Jinan, Shandong, China (Recruiting)
• Shandong Provincial Third Hospital — Jinan, Shandong, China (Recruiting)
• Jining First People's Hospital — Jining, Shandong, China (Recruiting)
• The First Affiliated Hospital of Ningbo University — Ningbo, Zhejiang, China (Recruiting)
• Beijing Tiantan Hopital, Capital Medical University — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Yuesong Pan

Conditions Alzheimers Disease; Alzheimers disease; Cervical Lymphatic Venous Anastomosis; Randomized Controlled Trial