Deep Cervical Lymphatlc-Venous Anastomosis Surgery for the Treatment of Alzheimer's Disease: A Pilot Study (DIVA Study)

Overview

The goal of this clinical trial is to To demonstrate the Safety and Efficacy of dcLVA Surgery for the Treatment of Alzheimer's Disease. Patients who meet the inclusion and exclusion criteria and consent to participate will be randomly assigned to either the experimental group (receiving dcLVA surgery plus standard medication) or the control group (receiving standard medication alone) Participants will: Undergo cognitive assessment and brain MRI assessment; Undergo a lumbar puncture; Undergo an injection of 20ml of gadodiamide contrast agent at a concentration of 0.5 mmol/L (1ml gadodiamide: 20ml 0.9% saline). Primary Outcome Measures: The change in the sum of Clinical Dementia Rating Scale (CDR) scores at 12-month in relative to baseline

Detailed description

This study aims to enroll patients diagnosed with AD. Patients who meet the inclusion and exclusion criteria and consent to participate will be randomly assigned to either the experimental group (receiving dcLVA surgery plus standard medication) or the control group (receiving standard medication alone). Following randomization, patients will undergo cognitive and brain MRI assessments, a lumbar puncture, and an injection of 20ml of gadodiamide contrast agent at a concentration of 0.5 mmol/L (1ml gadodiamide: 20ml 0.9% saline). MRI imaging scans will be conducted at 4 hours, 24 hours, and 48 hours post-injection to measure the dural signal unit ratio, which will be used to assess glymphatic clearance function. The study will track changes in cognitive function and glymphatic clearance function at baseline and during follow-up periods (7 days post-surgery, 6 months, and 12 months) and will evaluate the safety of the two treatment approaches.

Interventions

• Procedure Deep Cervical lymphatlc-Venous Anastomosis Surgery
  Cervical deep lymphatic-venous anastomosis (dcLVA) can promote the flow of cerebrospinal fluid within the glymphatic system. The procedure involves connecting deep cervical lymphatic vessels to veins, reducing pressure on lymph nodes and allowing lymphatic fluid from high-pressure vessels to flow into the lower-pressure venous system. This surgical intervention enhances the clearance of waste in the glymphatic system, particularly amyloid-beta (Aβ) and tau proteins. By facilitating the removal o
• Drug Lecanemab
  The newly approved anti-beta-amyloid (Aβ) monoclonal antibody Lecanemab can delay AD progression but is only suitable for patients in the early stages. For those with moderate to severe AD, Lecanemab is not effective.

Primary outcome measures

• The rate of change in the total score of the Clinical Dementia Rating Scale [Time frame: Time Frame: baseline,7 days post-surgery,3-month,6-month and 12-month]

Eligibility criteria

Inclusion criteria

• Diagnosed as an AD patient according to biological markers and clinical symptoms;
• Over 35 years old and with an MMSE or MOCA score ≤ 26;
• The patient or family member has signed an informed consent form.

Exclusion criteria

• Inability to cooperate with lumbar puncture;
• Cognitive impairment due to neurological infections (e.g., HIV, neurosyphilis, autoimmune encephalitis) or systemic diseases (e.g., diabetes, thyroid dysfunction);
• Significant organ dysfunction (heart, lung, liver, kidney);
• Coagulation disorders or contraindications to surgery;
• Inability to fully cooperate with follow-up visits.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhejiang Provincial People's Hospital — Hangzhou

Publications

• Zhao N, Wang Y, Yang S, Guo W, Li Z, Cao H, Zhang Z, Li Y, Chen D, Xia S, Xie Z, Qu Y, Wu Y, Li J, Yi L, Wang G, Guo M. Surgical Protocols for Deep Cervical Lymphovenous Anastomosis in a Rat Model: Lymph Node and Lymphatic Vessel Anastomoses. J Vis Exp. 2025 Nov 14;(225). doi: 10.3791/69201. PMID 41325201

Identifiers

NCT: NCT06530732 · KY2024106

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗