Clinical Study on Lymphaticovenous Anastomosis（LVA） for the Treatment of Alzheimer's Disease（AD）

Official title

Clinical Study on the Safety, Efficacy, and Mechanisms of Lymphaticovenous Anastomosis (LVA) for the Treatment of Alzheimer's Disease (AD)

Overview

The goal of this clinical trial is to explore the safety and efficacy of Lymphaticovenous Anastomosis (LVA) for the Treatment of Alzheimer's Disease (AD). The main questions it aims to answer are: 1. After LVA surgery treatment, do patients with AD show improvement in dementia, cognitive impairment, neurobehavioral symptoms? 2. What are the complications associated with LVA treatment for AD, including perioperative complications and long-term complications? 3. What is the mechanism of LVA treatment for AD patients, and what changes occur in AD-related biomarkers (Aβ42、 Aβ40、Aβ42/40、pTau217、pTau181) before and after surgery?

Interventions

• Procedure Lymphaticovenous Anastomosis
  The basic principle of LVA surgery is to anastomose the deep cervical lymphatic vessels of the brain with adjacent small veins, effectively enabling the direct reflow of accumulated Aβ and tau proteins in the brain's lymphatic circulation into the venous system, thereby improving the symptoms of Alzheimer's Disease (AD).

Primary outcome measures

• The assessment of score changes after Lymphaticovenous Anastomosis(LVA) for the treatment of Alzheimer's Disease(AD) using Mini-Mental State Examination(MMSE). [Time frame: From enrollment to the end of treatment at 3 days, 7 days, 1 month, 3 months, 6 months,1 year, 3 years, 5 years.]

Secondary outcome measures (1)

• The safety of Lymphaticovenous Anastomosis(LVA) for the Treatment of Alzheimer's Disease(AD) [Time frame: From enrollment to the end of treatment at 3 days, 7 days, 1 month, 3 months, 6 months, 1 year, 3 years, 5 years.]

Eligibility criteria

Inclusion criteria

• Patients diagnosed with Alzheimer's Disease based on biomarkers, imaging, and clinical symptoms;
• Male or female aged 50-85 years (inclusive);
• At least one caregiver who can live with the patient for an extended period;
• No severe systemic diseases affecting the heart, liver, kidneys, etc.;
• Patients who voluntarily participate in clinical recruitment, accept the LVA surgical treatment plan, and sign the informed consent form.

Exclusion criteria

• Poor overall health, unable to tolerate surgery;
• Preoperative anesthetic assessment indicates inability to tolerate general anesthesia;
• Presence of other neurological or psychiatric disorders;
• Severe bleeding tendency due to coagulopathy;
• Inability to comply with treatment and follow-up;
• Other conditions that preclude tolerance to surgery.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking university third hospital — Beijing

Publications

• Formolo DA, Yu J, Lin K, Tsang HWH, Ou H, Kranz GS, Yau SY. Leveraging the glymphatic and meningeal lymphatic systems as therapeutic strategies in Alzheimer's disease: an updated overview of nonpharmacological therapies. Mol Neurodegener. 2023 Apr 20;18(1):26. doi: 10.1186/s13024-023-00618-3. PMID 37081555
• Harrison IF, Ismail O, Machhada A, Colgan N, Ohene Y, Nahavandi P, Ahmed Z, Fisher A, Meftah S, Murray TK, Ottersen OP, Nagelhus EA, O'Neill MJ, Wells JA, Lythgoe MF. Impaired glymphatic function and clearance of tau in an Alzheimer's disease model. Brain. 2020 Aug 1;143(8):2576-2593. doi: 10.1093/brain/awaa179. PMID 32705145
• 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 2 PMID 30046111
• Huang SY, Zhang YR, Guo Y, Du J, Ren P, Wu BS, Feng JF; Alzheimer's Disease Neuroimaging Initiative; Cheng W, Yu JT. Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease. Alzheimers Dement. 2024 May;20(5):3251-3269. doi: 10.1002/alz.13789. Epub 2024 Mar 19. PMID 38501315
• Chachaj A, Gasiorowski K, Szuba A, Sieradzki A, Leszek J. The Lymphatic System In The Brain Clearance Mechanisms - New Therapeutic Perspectives For Alzheimer's Disease. Curr Neuropharmacol. 2023;21(2):380-391. doi: 10.2174/1570159X20666220411091332. PMID 35410605
• Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM. Alzheimer's disease. Lancet. 2016 Jul 30;388(10043):505-17. doi: 10.1016/S0140-6736(15)01124-1. Epub 2016 Feb 24. PMID 26921134
• Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study PMID 31248666
• Jia L, Du Y, Chu L, Zhang Z, Li F, Lyu D, Li Y, Li Y, Zhu M, Jiao H, Song Y, Shi Y, Zhang H, Gong M, Wei C, Tang Y, Fang B, Guo D, Wang F, Zhou A, Chu C, Zuo X, Yu Y, Yuan Q, Wang W, Li F, Shi S, Yang H, Zhou C, Liao Z, Lv Y, Li Y, Kan M, Zhao H, Wang S, Yang S, Li H, Liu Z, Wang Q, Qin W, Jia J; COAST Group. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adu PMID 33271079

Identifiers

NCT: NCT06918145 · IRB00006761-M20250166

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗