Clinical Trials Logo

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.


Clinical Trial 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. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05971030
Study type Interventional
Source Xuanwu Hospital, Beijing
Contact Yuqing Zhang
Phone 83198930
Email yuqzhang@vip.163.com
Status Recruiting
Phase N/A
Start date July 30, 2023
Completion date July 30, 2025

See also
  Status Clinical Trial Phase
Completed NCT04079803 - PTI-125 for Mild-to-moderate Alzheimer's Disease Patients Phase 2
Completed NCT04044495 - Sleep, Rhythms and Risk of Alzheimer's Disease N/A
Terminated NCT03052712 - Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies N/A
Recruiting NCT04520698 - Utilizing Palliative Leaders In Facilities to Transform Care for Alzheimer's Disease N/A
Active, not recruiting NCT04606420 - Can Lifestyle Changes Reverse Early-Stage Alzheimer's Disease N/A
Recruiting NCT05820919 - Enhancing Sleep Quality for Nursing Home Residents With Dementia - R33 Phase N/A
Terminated NCT03672474 - REGEnLIFE RGn530 - Feasibility Pilot N/A
Completed NCT03430648 - Is Tau Protein Linked to Mobility Function?
Recruiting NCT04949750 - Efficacy of Paper-based Cognitive Training in Vietnamese Patients With Early Alzheimer's Disease N/A
Recruiting NCT04522739 - Spironolactone Safety in African Americans With Mild Cognitive Impairment and Early Alzheimer's Disease Phase 4
Recruiting NCT05557409 - A Study to Assess the Efficacy and Safety of AXS-05 in Subjects With Alzheimer's Disease Agitation Phase 3
Recruiting NCT05288842 - Tanycytes in Alzheimer's Disease and Frontotemporal Dementia
Completed NCT06194552 - A Multiple Dose Study of the Safety and Pharmacokinetics of NTRX-07 Phase 1
Completed NCT03239561 - Evaluation of Tau Protein in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants Early Phase 1
Completed NCT03184467 - Clinical Trial to Evaluate the Efficacy and Safety of GV1001 in Alzheimer Patients Phase 2
Active, not recruiting NCT03676881 - Longitudinal Validation of a Computerized Cognitive Battery (Cognigram) in the Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease
Terminated NCT03487380 - Taxonomic and Functional Composition of the Intestinal Microbiome: a Predictor of Rapid Cognitive Decline in Patients With Alzheimer's Disease N/A
Completed NCT05538455 - Investigating ProCare4Life Impact on Quality of Life of Elderly Subjects With Neurodegenerative Diseases N/A
Recruiting NCT05328115 - A Study on the Safety, Tolerability and Immunogenicity of ALZ-101 in Participants With Early Alzheimer's Disease Phase 1
Completed NCT05562583 - SAGE-LEAF: Reducing Burden in Alzheimer's Disease Caregivers Through Positive Emotion Regulation and Virtual Support N/A