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

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

Study Overview

• Status: Recruiting
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Procedure: Deep Cervical lymphatlc-Venous Anastomosis Surgery; Drug: Lecanemab

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Sheng Zhang; Phone Number: +8618758188313; Email: zhangsheng@hmc.edu.cn
      • Principal Investigator: Sheng Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group; receiving dcLVA surgery plus standard medication	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 of these AD-associated proteins from the brain, dcLVA can reduce local tissue fibrosis and cervical nerve compression, potentially reversing degenerative changes, slowing disease progression, and improving the quality of life for AD patients.; 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.
Active Comparator: control group; receiving standard medication alone	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of change in the total score of the Clinical Dementia Rating Scale	The change in the sum of Clinical Dementia Rating Scale (CDR) scores at 12-month in relative to baseline , using the Chinese version of the CDR scale, with a score range of 0-3 points for each item.The total score ranges from a minimum of 0 points to a maximum of 18 points, where a higher score indicates a worse outcome.	Time Frame: baseline,7 days post-surgery,3-month,6-month and 12-month

Collaborators and Investigators

• Sponsor: Zhejiang Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: July 28, 2024
• First Submitted That Met QC Criteria: July 28, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: KY2024106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No