Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06448442 |
| Other study ID # |
2024-0429 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2024 |
| Est. completion date |
August 1, 2028 |
Study information
| Verified date |
June 2024 |
| Source |
Second Affiliated Hospital, School of Medicine, Zhejiang University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Alzheimer's disease (AD) is the most prevalent form of dementia, affecting 3-4% of the
population over a lifetime. It's characterized by abnormal Amyloid-beta (Aβ) and tau protein
expression and accumulation in the central nervous system, leading to amyloid plaques and
neurofibrillary tangles. While current treatments can slow cognitive decline, there's no
cure.
The discovery of the "glymphatic-meningeal lymphatic" system has shed new light on
cerebrospinal fluid circulation, showing it has a similar interstitial fluid system to
peripheral lymphatic circulation. This system helps clear waste and transport nutrients in
the brain, known as the glymphatic phenomenon. The deep cervical lymph nodes, part of this
system, are crucial for cerebrospinal fluid drainage and are linked to the clearance of
AD-related proteins.
Aging and inflammation can impair deep cervical lymph node function, increasing cerebrospinal
fluid drainage pressure and potentially contributing to AD progression. Lymphatic
anastomosis, a surgical technique used for lymphedema and other conditions, is being explored
as a potential treatment to alleviate neurodegenerative disease by reducing cerebrospinal
fluid pressure and clearing metabolic waste.
Description:
Alzheimer's disease (AD) is the most common form of dementia, with an estimated lifetime
prevalence rate of 3-4%. Its characteristics include abnormal expression of Amyloid-beta (Aβ)
and tau proteins, as well as their accumulation in the central nervous system. The aggregated
toxic proteins further form amyloid plaques and neurofibrillary tangles. One of the biggest
scientific and therapeutic challenges of AD is to elucidate this protein pathology and how it
leads to accumulation in the central nervous system. Although current drug treatment options
can slow down the decline in cognitive abilities, there is no treatment strategy to improve
the disease.
Recently, the revelation of the "glymphatic-meningeal lymphatic" system has updated the
latest theory of cerebrospinal fluid circulation. There is an interstitial fluid circulation
system in the brain tissue that is similar to peripheral lymphatic circulation. Research has
found that cerebrospinal fluid in the brain enters the perivascular space around the veins
through the perivascular space around the arteries, directed by the astrocyte Aquaporin
protein-4, which promotes the clearance of waste and the transport of nutrients in the brain,
a phenomenon known as the glymphatic phenomenon. At the same time, research has found that
there are a large number of lymphatic vessels on both sides of the dural venous sinuses,
which participate in the drainage of cerebrospinal fluid and eventually converge into the
deep cervical lymph nodes. In animal models of AD and Parkinson's disease (PD), the
"glymphatic-meningeal lymphatic" drainage function is significantly related to the clearance
of disease-related proteins such as amyloid beta (Aβ), tau, and alpha-synuclein. Ligation of
the deep cervical lymph nodes significantly exacerbates the progression of the disease. At
the same time, clinical studies have confirmed the decline of "glymphatic-meningeal
lymphatic" function in patients with AD and PD through magnetic resonance imaging technology.
The deep cervical lymph nodes play an important role as the final destination of
cerebrospinal fluid drainage in the "glymphatic-cranial lymphatic" system. With aging,
infection, and chronic inflammation, the function of the deep cervical lymph nodes gradually
declines, which will significantly increase the pressure of cerebrospinal fluid circulation
and reflux in the brain. The large amount of neurotoxic substances produced during the
progression of AD, will further lead to the dysfunction of the deep cervical lymph nodes,
ultimately leading to abnormal accumulation of toxic substances in the brain and the
progression of the disease. Lymphatic anastomosis is a surgical technique widely used for
limb lymphedema, post-traumatic chylous chest, breast cancer, and other post-tumor resection
local edema and other diseases, with high safety, reliability, and ease of operation, and has
been proven to have many advantages after half a century of testing. Currently, many
hospitals at home and abroad have carried out related operations, all of which have achieved
good results. Recently, only in our province, Zhejiang Provincial People's Hospital, Taizhou
Hospital, Hangzhou Qiushi Hospital, and others have carried out related operations, and the
famous Cleveland Clinic in the United States is also conducting related surgical treatment
research.
We speculate that anastomosing the corresponding lymphatic vessels in the neck with the veins
(Deep Cervical Lymph-Venous anastomosis) might reduce the cerebrospinal fluid circulation
pressure in the brain tissue, accelerate the return of interstitial fluid in the brain
tissue, clear the accumulation of metabolic products, and alleviate the progression of
neurodegenerative diseases.
