Clinical Study on Deep Cervical Lymphatic Trunk Decompression Combined With Mid-Cervical Deep Lymph Node-External Jugular Vein Anastomosis for Alzheimer's Disease Treatment

NCT06936514 | Enrolling By Invitation

• 1 other identifier: IRB2025-YX-099-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the feasibility, safety, and efficacy of bilateral deep cervical lymphatic trunk decompression combined with mid and deep cervical lymph node-extracervical vein anastomosis in the treatment of patients with Alzheimer's disease. The study seeks to explore new treatment options that may improve the quality of life for patients with Alzheimer's disease.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (5)

• Change in Alzheimer's disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog13)

  The Alzheimer's disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog 13) will be used to evaluate the general cognitive function. ADAS-Cog 13 ranges from 0 to 85, and higher value represents a worse outcome.

  From enrollment to the end of treatment at 3 days, 7 days, 1 month, 3 months.

• Change in Montreal Cognitive Assessment (MoCA)

  The Montreal Cognitive Assessment (MoCA) will be used to evaluate the general cognitive function. MoCA ranges from 0 to 30, and higher value represents a better outcome.

  From enrollment to the end of treatment at 3 days, 7 days, 1 month, 3 months.

• Change in Mini-mental State Examination (MMSE)

  The Mini-mental State Examination (MMSE) will be used to evaluate the general cognitive function. MMSE ranges from 0 to 30, and higher value represents a better outcome.

  From enrollment to the end of treatment at 3 days, 7 days, 1 month, 3 months.

• Change in Clinical Dementia Rating Scale sum of the boxes (CDR-SB)

  The Clinical Dementia Rating Scale sum of the boxes (CDR-SB) will be used to evaluate the general cognitive function. CDR-SB ranges from 0 to 18, and higher value represents a worse outcome.

  From enrollment to the end of treatment at 3 days, 7 days, 1 month, 3 months.

• Change in Clinical Dementia Rating Scale global score (CDR-GS)

  The Clinical Dementia Rating Scale global score (CDR-GS) will be used to evaluate the general cognitive function. CDR-GS ranges from 0 to 3, and higher value represents a worse outcome.

  From enrollment to the end of treatment at 3 days, 7 days, 1 month, 3 months.

Secondary Outcomes (1)

• Change in amyloid deposit in brain

  Baseline and 3 months after surgery

Study Arms (2)

Experimental group (Surgical group)

EXPERIMENTAL

bilateral cervical deep lymphatic trunk decompression combined with mid-cervical deep lymph node-external jugular vein anastomosis

Procedure: Bilateral Cervical Deep Lymphatic Trunk Decompression Combined with Mid-Cervical Deep Lymph Node-External Jugular Vein Anastomosis for Alzheimer's Disease

control group

NO INTERVENTION

Patients are not subject to surgical intervention, only medication is administered

Interventions

Bilateral Cervical Deep Lymphatic Trunk Decompression Combined with Mid-Cervical Deep Lymph Node-External Jugular Vein Anastomosis for Alzheimer's Disease PROCEDURE

This intervention involves a surgical approach that combines bilateral cervical deep lymphatic trunk decompression with mid-cervical deep lymph node-external jugular vein anastomosis (LVA) to enhance lymphatic drainage in Alzheimer's Disease (AD) patients. The aim is to reduce the accumulation of neurotoxic substances in the brain, potentially improving cognitive function by facilitating waste clearance via the lymphatic system. The procedure is intended to restore normal lymphatic flow, potentially slowing disease progression in AD patients who have moderate to severe cognitive impairment.

Experimental group (Surgical group)

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50-80 years;
• Meet the diagnostic criteria for AD in the Revised Criteria for the Diagnosis and Staging of Alzheimer's Disease (2024) published by the National Institute Aging and Alzheimer's Association (NIA-AA);
• Presence of moderate-to-severe cognitive impairment with a Clinical Dementia Rating (CDR) score ≥2, and Mini-Mental State Examination (MMSE) score of \< 20;
• Stable use of medication for ≥1 month and no planned change in medication within 3 months of randomisation;
• The patients and their families had been informed of the purpose, significance, expected effects and potential risks of the study and voluntarily participated in the study by providing biological samples and signing an informed consent form.

You may not qualify if:

• Dementia caused by other reasons: vascular dementia, central nervous system infections (e.g. HIV, syphilis, etc.), Creutzfeldt-Jakob disease, Huntington's chorea and Parkinson's disease, dementia with Lewy bodies, dementia due to traumatic brain injury, other physical and chemical factors (e.g. drug intoxication, alcohol intoxication, carbon monoxide intoxication, etc.), important physical diseases (e.g. hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial occupying lesions (e.g. subdural haematoma, brain tumour), endocrine system lesions (e.g. thyroid disease, parathyroid disease), and vitamin deficiency or any other cause of dementia;
• Presence of current serious or unstable medical conditions, including cardiovascular, hepatic, renal, gastrointestinal, respiratory, endocrine, neurological (except for cognitive impairment of AD origin), psychiatric, immunological or haematological disorders, and any other condition which, in the opinion of the investigator, may affect the results of the analyses in this study; or a life expectancy of \<24 months;
• Presence of a history of cancer within 5 years, with the exception of non-metastatic basal cell and/or squamous cell carcinoma of the skin, cervical carcinoma in situ, non-progressive prostate cancer, or other cancers with a low risk of recurrence or spread;
• Subjects who, in the judgement of the investigator, are actively suicidal and therefore considered to be at significant risk of suicide;
• Illiteracy or insufficient education to complete the scale assessment;
• A history of alcohol or drug abuse (other than a history of smoking) in the 2 years prior to the screening visit;
• A clinically significant history of multiple or severe drug allergies, significant atopic sensitivities, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme, linear IgA dermatosis, toxic epidermal necrolysis-relaxation, and/or exfoliative dermatitis);
• Clinically significant abnormalities of clinical significance (as determined by the investigator) on physical or neurological examination, vital signs, ECG, or clinical laboratory findings at screening that may be detrimental to the subject, interfere with the study, or suggest evidence of other causes of dementia;
• MRI results at screening that show evidence of significant abnormalities suggesting the presence of another potential etiology of progressive cognitive impairment or the presence of clinically significant findings which may compromise the subject's ability to safely participate in the study. For example, \>2 infarct foci \>2 cm in diameter; infarct foci in key areas such as thalamus, hippocampus, internal olfactory cortex, parafactory cortex, angular gyrus, cortex and other subcortical grey matter nuclei; and a Fazekas Scale grade of \>2 on the Cerebral White Matter Impairment Scale (CWMIS);
• Presence of any contraindication to MRI, including claustrophobia, or presence of prohibited metallic (ferromagnetic) implants/pacemakers;
• Presence of contraindications to LVA surgery, such as the presence of severe infection at the surgical site, severe cardiac, pulmonary, hepatic, renal, or other systemic functional abnormalities that cannot tolerate general anaesthesia surgery;
• Currently participating in a clinical trial involving other interventional clinical trials, or participating in any other type of medical research that is considered scientifically or medically incompatible with this study;
• Other reasons that prevent completion of this study: e.g., lack of a stable caregiver;
• Female subjects who are pregnant or planning to become pregnant;
• Patients with a Global Deterioration Scale (GDS) score of 7 were excluded, as the profound loss of verbal communication and basic motor function at this stage precluded adherence to study protocols and reliable participation in postoperative assessments.

Sponsors & Collaborators

• Oriental Neurosurgery Evidence-Based-Study Team: lead

Study Sites (1)

General Hospital of Tianjin Medical University, 154 Anshan Road, Heping District, Tianjin, China

Tianjin, China

Location

Related Publications (12)

• Benveniste H, Liu X, Koundal S, Sanggaard S, Lee H, Wardlaw J. The Glymphatic System and Waste Clearance with Brain Aging: A Review. Gerontology. 2019;65(2):106-119. doi: 10.1159/000490349. Epub 2018 Jul 11.

  PMID: 29996134 RESULT

• Goodman JR, Adham ZO, Woltjer RL, Lund AW, Iliff JJ. Characterization of dural sinus-associated lymphatic vasculature in human Alzheimer's dementia subjects. Brain Behav Immun. 2018 Oct;73:34-40. doi: 10.1016/j.bbi.2018.07.020. Epub 2018 Jul 25.

  PMID: 30055243 RESULT

• MohanaSundaram A, Mofatteh M, Ashraf GM, Pratico D. Glymphotherapeutics for Alzheimer's disease: Time to move the needle. Ageing Res Rev. 2024 Nov;101:102478. doi: 10.1016/j.arr.2024.102478. Epub 2024 Aug 31.

  PMID: 39222666 RESULT

• Guo X, Zhang G, Peng Q, Huang L, Zhang Z, Zhang Z. Emerging Roles of Meningeal Lymphatic Vessels in Alzheimer's Disease. J Alzheimers Dis. 2023;94(s1):S355-S366. doi: 10.3233/JAD-221016.

  PMID: 36683509 RESULT

• Jiang H, Wei H, Zhou Y, Xiao X, Zhou C, Ji X. Overview of the meningeal lymphatic vessels in aging and central nervous system disorders. Cell Biosci. 2022 Dec 17;12(1):202. doi: 10.1186/s13578-022-00942-z.

  PMID: 36528776 RESULT

• Wu Y, Zhang T, Li X, Wei Y, Li X, Wang S, Liu J, Li D, Wang S, Ye T. Borneol-driven meningeal lymphatic drainage clears amyloid-beta peptide to attenuate Alzheimer-like phenotype in mice. Theranostics. 2023 Jan 1;13(1):106-124. doi: 10.7150/thno.76133. eCollection 2023.

  PMID: 36593948 RESULT

• Zhang X, Cao R, Zhu C, Yang L, Zheng N, Ji W, Liu P, Chi T, Ji X, Zheng Z, Chen G, Zou L. Mechanism of anti-AD action of OAB-14 by enhancing the function of glymphatic system. Neurochem Int. 2023 Oct 27:105633. doi: 10.1016/j.neuint.2023.105633. Online ahead of print.

  PMID: 39491236 RESULT

• Chen Y, He X, Cai J, Li Q. Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases. J Biomed Res. 2024 Mar 2;38(3):206-221. doi: 10.7555/JBR.37.20230264.

  PMID: 38430054 RESULT

• Pu T, Zou W, Feng W, Zhang Y, Wang L, Wang H, Xiao M. Persistent Malfunction of Glymphatic and Meningeal Lymphatic Drainage in a Mouse Model of Subarachnoid Hemorrhage. Exp Neurobiol. 2019 Feb;28(1):104-118. doi: 10.5607/en.2019.28.1.104. Epub 2019 Feb 28.

  PMID: 30853828 RESULT

• Li G, Cao Y, Tang X, Huang J, Cai L, Zhou L. The meningeal lymphatic vessels and the glymphatic system: Potential therapeutic targets in neurological disorders. J Cereb Blood Flow Metab. 2022 Aug;42(8):1364-1382. doi: 10.1177/0271678X221098145. Epub 2022 Apr 28.

  PMID: 35484910 RESULT

• Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, Contarino C, Onengut-Gumuscu S, Farber E, Raper D, Viar KE, Powell RD, Baker W, Dabhi N, Bai R, Cao R, Hu S, Rich SS, Munson JM, Lopes MB, Overall CC, Acton ST, Kipnis J. Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease. Nature. 2018 Aug;560(7717):185-191. doi: 10.1038/s41586-018-0368-8. Epub 2018 Jul 25.

  PMID: 30046111 RESULT

• Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, Wiig H, Alitalo K. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015 Jun 29;212(7):991-9. doi: 10.1084/jem.20142290. Epub 2015 Jun 15.

  PMID: 26077718 RESULT

MeSH Terms

Interventions

Amyloid beta-Protein Precursor

Intervention Hierarchy (Ancestors)

Amyloidogenic Proteins; Amyloid; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Protein Precursors; Protease Nexins; Proteinase Inhibitory Proteins, Secretory

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2025
• First Posted: April 20, 2025
• Study Start: January 8, 2025
• Primary Completion: July 10, 2025
• Study Completion (Estimated): July 10, 2026
• Last Updated: February 19, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)