Deep neck lymphatic-to-vein surgery for Alzheimer's disease

Deep Cervical LymphatIc-Venous Anastomosis for Alzheimer's Disease (CLIVA-AD): a Prospective, Single-center, Randomized, Double Blinded Trial

This trial will try a deep neck lymphatic-to-vein surgical procedure in people aged 50–80 with biomarker-confirmed mild cognitive impairment or mild-to-moderate Alzheimer's disease to see if it improves symptoms.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 50 Years to 80 Years
• Sex: All
• Sponsor: General Hospital of Shenyang Military Region (other)
• Drugs / interventions: Lecanemab, Donanemab
• Locations: 1 site (Shenyang)
• Trial ID: NCT07294885 on ClinicalTrials.gov

What this trial studies

Investigators perform deep cervical lymphatic-venous anastomosis, a microsurgical technique that connects lymphatic vessels to nearby veins to attempt to restore intracranial lymphatic drainage. The procedure is relatively minimally invasive and has been used for peripheral lymphedema treatment. Animal studies and small clinical series in China have reported early postoperative improvements in mood, memory, executive function, and communication, but those benefits were often transient and not sustained. This trial enrolls adults 50–80 with biomarker-confirmed AD (positive amyloid and tau PET or CSF) and MMSE 12–26, and excludes people with contraindications to imaging, surgery, anesthesia, or major organ dysfunction.

Who should consider this trial

Good fit: Ideal candidates are adults 50–80 years old with biomarker-confirmed mild cognitive impairment or mild-to-moderate Alzheimer's disease, MMSE 12–26, at least six months disease duration, and a reliable caregiver.

Not a fit: Patients with advanced dementia, lack of AD biomarker confirmation, contraindications to MRI/PET/ICG or to surgery/anesthesia, or significant comorbid organ dysfunction are unlikely to benefit.

Why it matters

Potential benefit: If successful, the surgery could produce lasting improvements in cognitive and neuropsychiatric symptoms by improving intracranial lymphatic clearance.

How similar studies have performed: Animal experiments and small clinical reports from China have shown early transient symptomatic improvements after deep cervical lymphatic-venous anastomosis, but controlled evidence of sustained benefit in humans is lacking.

Eligibility criteria

Inclusion Criteria:

* Age 50-80 years (inclusive), regardless of gender.
* Meeting the diagnostic criteria for Mild Cognitive Impairment or mild to moderate dementia due to Alzheimer's disease (according to the 2024 AA clinical diagnostic criteria for AD-related dementia).
* Disease duration of 6 months or longer, with no clinical improvement after 3 months or more of conservative treatment.
* MMSE score: 12-26.
* Biomarker confirmation of AD: positive Aβ-PET and tau-PET, or positive cerebrospinal fluid biomarkers.
* Having a reliable caregiver (providing companionship for ≥3 hours per day).
* Signed written informed consent from the patient or legally authorized representative.

Exclusion Criteria:

* Contraindications to MRI, ICG angiography, or PET.
* Contraindications to surgery or anesthesia, such as coagulation disorders (platelet count \<100×10⁹/L, INR \>1.7).
* Comorbid major organ dysfunction, such as reduced left ventricular ejection fraction, severe hepatic or renal insufficiency (AST or ALT \>3 times the upper limit of normal; eGFR \<30 mL/min/1.73m²).
* Intracranial structural lesions indicated by MRI, including brain tumors, cerebral infarction, intracranial hemorrhage, aneurysms, arteriovenous malformations, hydrocephalus, etc.
* MRI findings suggestive of significant cerebral small vessel disease features: more than one lacunar infarction in the deep white matter and periventricular regions and/or white matter hyperintensity (WMH) with a Fazekas grade \>2, or the presence of ≥4 cerebral microbleeds.
* Other causes of dementia, such as hypothyroidism or vitamin B12 deficiency.
* Drug/alcohol addiction.
* Severe psychiatric illness or suicide risk.
* Comorbid medical conditions with a life expectancy of less than 1 year.
* Participation in another interventional trial within the past 3 months.
* Poor compliance or judged by the investigator as unsuitable for participation.
* Patients receiving therapy with Lecanemab or Donanemab.
* Other conditions that the researcher deems unsuitable for participation in this study.

Where this trial is running

Shenyang

• Department of Neurology, General Hospital of Northern Theater Command — Shenyang, China (RECRUITING)

Conditions: Alzheimer Disease