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

NCT07094438 | Recruiting Phase 1 DMC

• 1 other identifier: ChinaPLAGH_CNT
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog)

  The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) scale is widely used for evaluating the severity of AD. ADAS-Cog consists of 12 components including word recall, naming, command, constructional praxis, ideational praxis, orientation, word recognition, remembering test instructions, spoken language ability, word finding difficulty, comprehension of oral language, and attention. The ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and orientation. ADAS-Cog score ranges from 0-75, with higher scores indicating more severe cognitive impairment.

  changes of baseline and month 1, month 3, month 6, month 9, month 12, month 15, month 18 after surgery

• Mini-Mental State Examination (MMSE) score

  Mini-Mental State Examination (MMSE) is one of the most influential cognitive screening tools worldwide. It consists of five dimensions including orientation (10 points), registration (3 points), attention and calculation (5 points), recall (3 points) and language and praxis (9 points). Educational attainment level-related dementia classification: illiterate: 5 points ≤ MMSE score ≤16 points; primary school: 8 points ≤ MMSE score ≤ 20 points; junior high school and above: 10 points ≤ MMSE score ≤ 24 points.

  changes of baseline and month 1,month 3, month 6, month 9, month 12 month 15, month 18 after surgery

• Clinical Dementia Rating(CDR) score

  The Clinical Dementia Rating(CDR) is 5-point scale used to characterize six domains (memory, orientation, judgment \& problem solving, community affairs, home \& hobbies and personal care) of the cognitive and functional performance of the aged (in particular AD patients). Patients are rated on dementia severity: 0 = normal, 0.5 = questionable dementia; 1 = mild dementia; 2 = moderate dementia; 3 = severe dementia.

  changes of baseline and month 1, month 3, month 6, month 9, month 12, month 15, month 18 after surgery

Study Arms (3)

DBS arm

EXPERIMENTAL

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

Procedure: Deep Brain Stimulation, DBS

LVA arm

EXPERIMENTAL

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

Procedure: Deep cervical lymphatic-venous anastomosis, LVA

medication arm

ACTIVE COMPARATOR

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

Drug: Recognized pharmacological treatments for AD.

Interventions

Deep Brain Stimulation, DBS 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.

DBS arm

Deep cervical lymphatic-venous anastomosis, LVA 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.

LVA arm

Recognized pharmacological treatments for AD. DRUG

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

medication arm

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Zhiqi Mao, Ph.D

  Chinese PLA General Hospita

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiqi Mao, Ph.D

CONTACT

8618910155994; markmaoqi@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: July 30, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 30, 2025

Record last verified: 2025-07

Locations

CN (1)