Robotic-assisted microsurgery to improve neck lymphatic clearance in Alzheimer's disease

Robotic-Enabled Microsurgical Intervention for Neurodegenerative Disease - A Global, Prospective, Early Feasibility Study in Alzheimer's Patients

This study will test whether robotic-assisted microsurgery on deep neck lymph nodes can safely help people 50 and older with mild to moderate Alzheimer's disease who also have neck lymphatic problems.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: MMI (Medical Microinstruments, Inc.) (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 2 sites (Palo Alto, California and 1 other locations)
• Trial ID: NCT07178210 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter early-feasibility investigational device exemption (IDE) study using the Symani robotic surgical system to perform microsurgical techniques in the deep cervical lymph node (dCLN) region. Participants will have biomarker-confirmed mild to moderate Alzheimer's disease and imaging-confirmed extracranial lymphatic abnormalities and must be judged suitable for lymphatic surgery. The procedure uses robotic-assisted microsurgical anastomosis in the dCLN region with perioperative safety monitoring and serial clinical and biomarker follow-up. Outcomes focus on procedural feasibility, safety, and signals of improved clearance of neurotoxins such as amyloid-beta and phosphorylated tau.

Who should consider this trial

Good fit: Ideal candidates are adults aged 50 or older with biomarker-positive mild to moderate Alzheimer's disease (within the specified MMSE and CDR-SB ranges), imaging-confirmed head/neck extracranial lymphatic abnormalities, and who are deemed suitable for robotic-assisted lymphatic surgery and consent to follow-up.

Not a fit: Patients without extracranial lymphatic abnormalities, without positive amyloid biomarkers, with advanced Alzheimer's disease, or who are not surgical candidates are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the procedure could increase clearance of amyloid and tau from the brain and potentially slow cognitive decline in some patients.

How similar studies have performed: Applying microsurgical lymphatic techniques to Alzheimer's is novel and largely untested, though similar microsurgical approaches have shown success treating peripheral lymphedema.

Eligibility criteria

Inclusion Criteria:

1. Patient aged 50 or older
2. Patient has confirmed mild to moderate Alzheimer's Disease according to the National Institute of Aging-Alzheimer's Association (NIA-AA) criteria
3. Patient has a positive amyloid PET test and/or a positive CSF t-tau/amyloid-beta-42 test
4. Patient has an MMSE score within the mild to moderate range (21-26 and 10-20)
5. Patient has CDR-SB score within the mild to moderate range; mild is 4.5to 9.0 and moderate is 9.5 to 15.5
6. Patient has confirmed extracranial lymphatic abnormalities in the head and neck region as identified by preoperative imaging
7. Investigator deems the candidate acceptable for lymphatic surgery with a robotic-assisted microsurgical anastomosis in accordance with the Symani System's Instructions for Use (IFU)
8. Patient or their legally authorized representative agrees to participate in the study, return for all required follow-up visits, complete all study procedures, and has willingly provided written informed consent after receiving all information related to the study, its requirements, and the robotic assisted procedure

Exclusion Criteria:

1. Patient (or their legally authorized representative) is unwilling to provide informed consent
2. Patient has suspected dementia of other type, e.g., Lewy body, frontotemporal disorder, vascular, etc.
3. Patient has documented or suspected neurological or intracranial conditions such as cerebrovascular accident, tumors, intracranial space occupying lesions, seizures or other intracranial/neurological conditions that may affect their safety in the study.
4. History of head and neck radiation exposure
5. Patient with severe kidney disease (GFR \<30 mL/min/1.73m2)
6. Patient with acute kidney injury
7. Active systemic infection under treatment with intravenous antibiotics
8. Patient has a modified Rankin Score (mRS) of \>4
9. Clinically significant cardiovascular, digestive, respiratory, endocrine, or central nervous system disorders, previous mental disorders, or other disorders that may significantly affect the data collection or the ability to comply with the protocol per the investigator's discretion
10. Known history of significant bleeding, coagulopathy, or Von Willebrand's disease
11. Patient with an active cancer diagnosis and/or currently receiving treatment for cancer or has received treatment within the past 6 months
12. Patient is currently receiving treatment or has been treated with anti-amyloid-beta monoclonal antibody therapy within the past 3 months
13. Patient has contraindication for MRI or intrathecal administration of gadobutrol
14. Currently enrolled in any other investigational clinical studies that the investigator believes may impact patient safety or study outcomes
15. Patient is ineligible to participate for other reasons in the judgment of the investigator

Where this trial is running

Palo Alto, California and 1 other locations

• Stanford Medical Center — Palo Alto, California, United States (Recruiting)
• Baptist Health Research Institute — Jacksonville, Florida, United States (Recruiting)

Study contacts

• Study coordinator: Clinical Operations

Conditions Alzheimer Disease; Lymphatic Obstruction