Alzheimer's Disease Treated With Vagus Nerve Stimulation

NCT ID: NCT06923007

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-07
• Study Completion Date: 2027-12-31

Brief Summary

The goal of this clinical trial is to evaluate the safety and efficacy of vagus nerve stimulation (VNS) for treating Alzheimer's disease (AD) in patients aged 50-80 years with mild cognitive impairment to moderate Alzheimer's disease. The main questions it aims to answer are:

Is the change from baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) score at 6 months post-randomization better in the VNS group compared to the sham stimulation group? Is the change from baseline in scores of other cognitive function, neuropsychiatric symptom, or activities of daily living scales at 6 months post-randomization better in the VNS group compared to the sham stimulation group? Researchers will compare the group receiving vagus nerve stimulation (active VNS group) and the group receiving sham vagus nerve stimulation (sham VNS group) to see if VNS is more effective in improving cognitive function, neuropsychiatric symptoms, or activities of daily living.

Participants will:

Undergo screening assessments (including medical history, physical exams, cognitive and behavioral scale assessments, imaging, etc.).

Undergo surgery for VNS device implantation. Be randomized to either the active VNS or sham VNS group and receive the corresponding stimulation treatment for 6 months (while continuing standard AD medication).

Attend multiple follow-up visits during the study (baseline, randomization day, 3 months, and 6 months post-randomization) for clinical scale assessments.

Potentially provide biological samples (blood, CSF) and undergo additional auxiliary examinations (e.g., MRI, EEG, PET) at specific time points.

Conditions

Alzheimer Disease (AD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vague nerve stimulation group

Participants receive active vagus nerve stimulation (VNS) for 6 months.

Group Type: EXPERIMENTAL

Vagus Nerve Stimulation

Intervention Type: DEVICE

After randomization, VNS is performed for 6 months. The stimulation parameters will be 30 Hz and 250 μs, the maximum tolerable current is selected according to the patients' adverse reactions (dizziness, palpitations, abnormal sensations, local pain, etc.), and the recommended treatment intensity is 0.8 mA.

Sham VNS group

Participants receive sham vagus nerve stimulation for 6 months.

Group Type: SHAM_COMPARATOR

Sham Vagus Nerve Stimulation

Intervention Type: DEVICE

After randomization, sham vagus nerve stimulation VNS treatment is performed for 6 months. The stimulation parameters will be 30 Hz, 250 μs, and the treatment intensity will be 0 mA.

Interventions

Vagus Nerve Stimulation

After randomization, VNS is performed for 6 months. The stimulation parameters will be 30 Hz and 250 μs, the maximum tolerable current is selected according to the patients' adverse reactions (dizziness, palpitations, abnormal sensations, local pain, etc.), and the recommended treatment intensity is 0.8 mA.

Intervention Type: DEVICE

Sham Vagus Nerve Stimulation

After randomization, sham vagus nerve stimulation VNS treatment is performed for 6 months. The stimulation parameters will be 30 Hz, 250 μs, and the treatment intensity will be 0 mA.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Age: 50-80 years

2. Subjects conform to the diagnostic criteria for AD established by the National Institute on Aging and the Alzheimer's Association [National Institution Aging and Alzheimer's Association (NIA-AA)]

3. There is mild to moderate cognitive impairment, and the clinical cognitive rating scale [Clinical Dementia Rating (CDR)] score is 0.5-2.

4. Stable use of the drug for more than 1 month, and no plan to change the medication within 6 months after randomization

5. The informed consent form is signed, and the patient complies with the requirements.

Exclusion Criteria

1. Dementia caused by other reasons, including vascular dementia, central nervous system infections (such as AIDS, syphilis, etc.), Creutzfeldt-Jakob disease, Huntington's disease and Parkinson's disease, dementia with Lewy bodies, traumatic brain injury dementia, other physical and chemical factors (such as drug poisoning, alcohol poisoning, carbon monoxide poisoning, etc.), significant physical illnesses (such as hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space-occupying lesions (such as subdural hematoma, brain tumor), endocrine system disorders (such as thyroid disease, parathyroid disease), and dementia due to vitamin deficiency or any other cause.

2. The presence of a serious or unstable disease, including cardiovascular, liver, kidney, gastrointestinal, respiratory, endocrine, neurological (AD-derived cognitive impairment excluded), psychiatric, immune or blood disorders, and other diseases that the investigator considers may affect the analysis results of this study, or life expectancy < 24 months.

3. A history of cancer within 5 years, except for non-metastatic basal cell carcinoma and/or squamous cell carcinoma, cervical carcinoma in situ, non-progressive prostate cancer, or other cancers with low risk of recurrence or spread.

4. The subject has been diagnosed with any primary mental disorder other than AD-related cognitive impairment. If the investigator deems that the presence of this mental disorder or symptom may affect the interpretation of VNS efficacy, cognitive assessment, or the subject's ability to complete the study, then the subject imust be excluded. Subjects with a history of schizophrenia or other chronic psychiatric conditions are also excluded.

5. Subjects who are judged by the investigator to have suicidal tendencies

6. Illiteracy or insufficient education to complete the scale assessment

7. Having a history of alcohol or drug abuse (excluding smoking history) within 2 years prior to the screening visit

8. A history of multiple or severe drug allergy, obvious atopic allergic constitution or severe hypersensitivity after treatment (including but not limited to severe polymorphic erythema, linear IgA dermatosis, toxic epidermal necrolysis and/or exfoliative dermatitis) with clinical significance

9. Important abnormalities that may be clinically significant and harmful to the subject, affect the study, or suggest other evidence of etiology of dementia during screening, such as physical examination or neurological examination, vital signs, ECG or clinical laboratory test results (determined by the investigator)

10. Screening MRI results showing significant abnormalities suggest another potential cause of progressive cognitive impairment, or findings with clinical significance that may affect the participants ability to safely participate in the study. For example, more than two infarcts larger than 2 cm in diameter, infarcts in critical areas such as the thalamus, hippocampus, internal olfactory cortex, parahippocampal cortex, angular gyrus, or other gray matter nuclei in the subcortical regions, as well as a score of > 2 on the Fazekas Scale

11. Any MRI contraindications, including claustrophobia, or the presence of prohibited metal (ferromagnetic) implant/cardiac pacemakers

12. There are contraindications for VNS surgery, such as left vagus nerve injury, severe infection at the surgical site, and severe heart, lung, liver, kidney or other system dysfunction that cannot tolerate general anesthesia surgery.

13. Currently participating in other interventional clinical trials, or any other type of medical research that is considered scientifically or medically incompatible with this study

14. Other reasons that hinder the completion of this study, such as lack of stable caregivers

15. Female subjects who are pregnant or planning to become pregnant

16. Research center staff members and/or their immediate family members directly related to this study. Immediate family members are spouses, parents, children, or siblings, whether biological or legally adopted relatives.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Municipal Administration of Hospitals

OTHER_GOV

Sponsor Role: lead

Responsible Party

Zhang Jianguo

Director of functional neurosurgery in Beijing Tiantan Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianguo Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Wei Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Locations

Beijing Tiantan Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Rujin Wang

Role: CONTACT

644848346@qq.com

+86 18101287707

Facility Contacts

Rujin Wang

Role: primary

644848346@qq.com

+86 18101287707

Other Identifiers

ZLRK202313

Identifier Type: -

Identifier Source: org_study_id