Deep Cervical LymphatIc-Venous Anastomosis for Alzheimer's Disease (CLIVA-AD): a Prospective, Single-center, Randomized, Double Blinded Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 50
- Primary Endpoint
- Changes in Montreal Cognitive Assessment (MoCA) score
Study Overview
Brief Summary
Lymphaticovenous anastomosis (LVA) is a microsurgical technique that involves anastomosing fine lymphatic vessels with adjacent veins to reestablish lymphatic drainage pathways. It is used in the treatment of lymphedema-related conditions and is characterized by minimal invasiveness and rapid recovery. Based on findings from animal studies, some physicians in China have attempted deep cervical lymphatic-venous anastomosis to improve intracranial lymphatic drainage in patients with Alzheimer's disease (AD). Most studies, including those from our center, have observed early postoperative improvements in various domains such as mood, memory, executive function, and communication abilities in the majority of patients. However, these symptomatic improvements are not sustained. The reasons for the early improvements remain unclear. Are they due to enhanced lymphatic drainage resulting from the surgery itself, or are they attributable to other factors such as anesthetic effects, vascular release, or modulation of sympathetic nerves? Therefore, it is necessary to conduct a randomized controlled trial with a sham surgery group to clarify the causes of early clinical symptom improvements. Based on this, this project aims to carry out a prospective, single-center, randomized double-blind controlled study to evaluate whether the early symptomatic improvements following deep cervical LVA in AD patients are attributable to the surgical intervention itself or to other aspects of the procedure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- 50 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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.
Arms & Interventions
LVA group
patients will receive lymphaticovenous anastomosis
Intervention: deep cervical lymphaticovenous anastomosis (Procedure)
Sham group
patients will undergo the LVA surgical procedure without performing the lymphaticovenous anastomosis.
Intervention: deep cervical lymphaticovenous anastomosis (Procedure)
Outcomes
Primary Outcomes
Changes in Montreal Cognitive Assessment (MoCA) score
Time Frame: 4±1 days
MoCA ranges from 0 to 30, with higher score meaning better outcome
Changes in Mini-mental State Examination (MMSE) score
Time Frame: 4±1 days
MMSE ranges from 0 to 30, with higher score meaning better outcome
Changes in Barthel index (BI)
Time Frame: 4±1 days
BI ranges from 0 to 100, with higher score meaning better outcome
Changes in Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus)
Time Frame: 4±1 days
CIBIC-plus ranges from 1 to 7, with higher score meaning worse outcome
Secondary Outcomes
- Severe adverse events(Perioperative period)
- Changes in Montreal Cognitive Assessment (MoCA) score(90±7 days; 180±15 days; 270±20 days)
- Changes in Mini-mental State Examination (MMSE) score(90±7 days; 180±15 days; 270±20 days)
- Changes in Barthel index (BI)(90±7 days; 180±15 days; 270±20 days)
- Changes in Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus)(90±7 days; 180±15 days; 270±20 days)
Investigators
Hui-Sheng Chen
Director
General Hospital of Shenyang Military Region