Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05971030 |
| Other study ID # |
2023062 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 30, 2023 |
| Est. completion date |
July 30, 2025 |
Study information
| Verified date |
June 2023 |
| Source |
Xuanwu Hospital, Beijing |
| Contact |
Yuqing Zhang |
| Phone |
83198930 |
| Email |
yuqzhang[@]vip.163.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive
cognitive impairment and memory impairment, and is also a major cause of global dementia,
characterized by progressive decline in memory and daily living behavior. The incidence rate
of AD increases with age. The prevalence rate of AD among men over 65 years old in China is
3.4%, and that of women is 7.7%, with a total prevalence rate of 5.9%. Among them, people
over 65 years old can live for an average of 4 to 8 years after being diagnosed with
Alzheimer's disease. According to statistics, there were approximately 5.98 million AD
patients in China in 2005, reaching 10.2 million in 2020 and 22.5 million by 2040, making it
the largest country with AD.
At present, the treatment of AD is mostly limited to drug therapy, including Acetylcholine
enzyme inhibitor, N-methyl-D-aspartate receptor antagonist and brain cell metabolism
promoter. Although there are many types of drugs, their efficacy is not satisfactory, as they
not only cannot effectively prevent and cure AD, but also cannot slow down the progression of
AD. Regarding the surgical treatment of AD, neuromodulatory surgery, especially DBS (Deep
Brain Electrical Stimulation), involves implanting stimulation electrodes into deep neural
nuclei in the brain and performing electrical stimulation to change the excitability of the
corresponding nuclei or neural circuits, and has been included in alternative treatment
plans. In the past 20 years, DBS technology has been continuously explored for the treatment
of AD, but an increasing number of clinical trials have shown that there is no effective
target for AD-DBS. Therefore, there is an urgent need for new treatment methods to improve
the current treatment status.
Description:
The main principle of DBS is to regulate the activity of neural components by implanting
electrodes into key brain regions using a built-in pulse generator. The basic principle of
using DBS in AD is that AD is not only a neurodegenerative disease, but also a neural circuit
disease, because it affects several integrated cortical and subcortical pathways, especially
those involving memory and cognition. DBS implants stimulation electrodes into deep neural
nuclei in the brain for electrical stimulation, altering the excitability of the
corresponding nuclei or neural circuits, which may lead to therapeutic effects. However, the
stimulation targets of the electrodes are still unclear.
There are currently 3 clinical studies on AD-DBS reported in the literature, using
stimulation targets such as the Basal Nucleus of Meynert (NBM) and the fornix. One of the
studies was reported this year by a team from Kuhn et al. in Germany. They used NBM as a
stimulation target and treated 6 patients with DBS. The stimulation lasted for 12 months and
was evaluated using the Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS Co g)
and the Simplified Mental State Examination Scale (MMSE). Among them, one patient showed
improvement in their ADAS Log score, two patients stabilized, and three patients continued to
deteriorate in cognitive function. The other was a phase I clinical trial conducted by the
Lozano team in Canada in 2010. The team used the fornix as a stimulation target to perform
DBS treatment on 6 mild AD patients, with the same stimulation for 12 months. The results
showed that only 1 out of 6 patients had significant improvement in cognitive function
(reduced ADAS Cog score), while the remaining 5 patients still showed varying degrees of
deterioration. In addition, Fontaine et al. reported in 2013 on a patient with transfornix
electrical stimulation, where 12 months of continuous electrical stimulation stabilized the
patient's MMSE and ADAS-Log scores. However, the above three studies all found that DBS can
improve the glucose metabolism level of brain tissues in temporal and parietal lobes. The
above studies indicate that although NBM and fornix electrical stimulation have some
improvement in cognitive function in some AD patients, the overall improvement rate is low,
with most patients in an unresponsive state. Therefore, given the core position of
stimulation targets in deep brain electrical stimulation surgery, it is urgent to explore new
stimulation targets in order to improve the efficacy of DBS. The combination of medial
prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) can serve as an ideal
stimulation target At present, the treatment of AD is still a global challenge, but the
non-invasive neural regulation techniques (rTMS and tDCS) based on the medial prefrontal
cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) have preliminarily confirmed that
mPFC and dlPFC regions may be potential therapeutic targets for AD, which can significantly
improve the cognitive status of therapists. At present, the targets used for treating AD with
DBS are the fornix and NBM, but the effectiveness of treating AD has not been confirmed.
Based on a thorough analysis of current international research and in conjunction with
previous research conducted by our center, the investigators propose to combine the left mPFC
and dlPFC regions as stimulation targets and innovatively use sheet electrodes for cortical
brain stimulation (CBS), which is well established. As a stimulation method of DBS, CBS
stimulates the cortex relative to the deep stimulation target. For example, common pain
electrical stimulation uses CBS, so the cortical electrical stimulation in this study adopts
the naming method of CBS. On this basis, the investigators strictly set inclusion and
exclusion criteria to ensure the quality of enrolled patients, and conducted thorough
experimental design and validated the efficacy of CBS in treating AD from multiple
perspectives using specific memory and cognitive function assessment scales, fusion function,
structure, metabolic brain networks, and other methods.
