Study Safety and Efficacy of Deep Brain Stimulation (DBS) and Cervical Deep Lymphoid-venous Anastomosis (LVA) in Alzheimer's Disease

NCT ID: NCT07094438

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2027-07-31

Brief Summary

To investigate the safety of deep brain stimulation (DBS) and cervical deep lymphoid-venous anastomosis (LVA) in the treatment of severe Alzheimer's disease (AD); to investigate the effectiveness of DBS and LVA in the treatment of severe AD, i.e., effects of deep brain stimulation on cognitive function, emotion and life quality in patients with severe AD.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

DBS arm

Patients in the DBS group underwent deep brain electrode implantation, followed by cranial MRI and CT to verify the accuracy of electrode placement.

Group Type: EXPERIMENTAL

Deep Brain Stimulation, DBS

Intervention Type: PROCEDURE

Deep brain stimulation (DBS) is performed after preoperative MRI and CT images are fused in a planning system to determine the target and trajectory. Under general anesthesia, electrodes are precisely implanted into the fornix or nucleus basalis of Meynert using a stereotactic frame or neurosurgical robot. The electrodes are inserted through a burr hole in the patient's skull and connected to a pulse generator placed subcutaneously in the chest. Optimal stimulation parameters for Alzheimer's disease are not yet established. For fornix targets, settings are typically 3-3.5 V, \~130 Hz, 90 μs; for nucleus basalis targets, 2-4.5 V, 10-20 Hz, 90-150 μs, adjusted according to anatomical features and intraoperative responses.

LVA arm

Patients in the LVA group underwent LVA surgery, followed by cervical ultrasound and CT to assess the anastomosis.

Group Type: EXPERIMENTAL

Deep cervical lymphatic-venous anastomosis, LVA

Intervention Type: PROCEDURE

Cervical deep lymphaticovenous anastomosis (LVA) microsurgically connects deep cervical lymphatic vessels to adjacent veins, promoting drainage of brain-derived amyloid-β and tau into the venous system and potentially alleviating Alzheimer's disease symptoms. The minimally invasive neck procedure involves small incisions and high-magnification suturing of lymphatics and veins with ultra-fine (11-0 or 12-0) sutures, creating multiple anastomoses to enhance brain lymphatic outflow.

medication arm

Patients in the medication group received drug therapy only, without undergoing surgery.

Group Type: ACTIVE_COMPARATOR

Recognized pharmacological treatments for AD.

Intervention Type: DRUG

Patients in the medication group received only the currently recognized pharmacological treatments for AD, including Memantine Hydrochloride and Donepezil.

Interventions

Deep Brain Stimulation, DBS

Deep brain stimulation (DBS) is performed after preoperative MRI and CT images are fused in a planning system to determine the target and trajectory. Under general anesthesia, electrodes are precisely implanted into the fornix or nucleus basalis of Meynert using a stereotactic frame or neurosurgical robot. The electrodes are inserted through a burr hole in the patient's skull and connected to a pulse generator placed subcutaneously in the chest. Optimal stimulation parameters for Alzheimer's disease are not yet established. For fornix targets, settings are typically 3-3.5 V, \~130 Hz, 90 μs; for nucleus basalis targets, 2-4.5 V, 10-20 Hz, 90-150 μs, adjusted according to anatomical features and intraoperative responses.

Intervention Type: PROCEDURE

Deep cervical lymphatic-venous anastomosis, LVA

Cervical deep lymphaticovenous anastomosis (LVA) microsurgically connects deep cervical lymphatic vessels to adjacent veins, promoting drainage of brain-derived amyloid-β and tau into the venous system and potentially alleviating Alzheimer's disease symptoms. The minimally invasive neck procedure involves small incisions and high-magnification suturing of lymphatics and veins with ultra-fine (11-0 or 12-0) sutures, creating multiple anastomoses to enhance brain lymphatic outflow.

Intervention Type: PROCEDURE

Recognized pharmacological treatments for AD.

Patients in the medication group received only the currently recognized pharmacological treatments for AD, including Memantine Hydrochloride and Donepezil.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Meeting the diagnostic criteria for dementia formulated by the National Institute on Aging-Alzheimer's Association (NIA-AA).
• Clinical Dementia Rating (CDR) score of 3 points.
• Ability to ambulate independently or with the aid of a walker/cane.
• Adequate visual and auditory capacity to cooperate with examinations and treatment.
• Voluntary participation with written informed consent provided by both the subject and their legal guardian.

Exclusion Criteria

• Pre-existing abnormal brain structure (e.g., tumor, cerebral infarction, hydrocephalus, or intracranial hemorrhage).
• Comorbidity with other neurological disorders such as multiple sclerosis, epilepsy, or Parkinson's disease.
• Psychiatric disorders: e.g., anxiety, depression, other affective disorders, or drug-induced psychosis.
• Severe internal diseases, currently using respiratory/cardiovascular/anticonvulsant/psychotropic drugs, or clinically significant gastrointestinal, renal, hepatic, respiratory, infectious, endocrine, or cardiovascular diseases, cancer, alcoholism, or substance addiction.
• Severe auditory or visual impairment.
• Clinical comorbidities with life expectancy <2 years.
• History of cranial surgery.
• Contraindications to MRI or transcranial alternating current stimulation (tACS) (e.g., cardiac pacemaker, post-deep brain stimulation surgery).
• Eczema or sensitive skin.
• Familial Alzheimer's disease.
• Other types of dementia: e.g., vascular dementia, Lewy body dementia, frontotemporal dementia, or infectious dementia;
• Any other condition deemed by the investigator as unsuitable for the study

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhiqi Mao

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiqi Mao, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospita

Locations

Chinese PLA General Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhiqi Mao, Ph.D

Role: CONTACT

markmaoqi@126.com

8618910155994

Facility Contacts

Zhiqi Mao, Ph.D

Role: primary

markmaoqi@126.com

8618910155994

Other Identifiers

ChinaPLAGH_CNT

Identifier Type: -

Identifier Source: org_study_id