Vagus nerve stimulation to improve cognition in people with mild-to-moderate Alzheimer's disease

Study on the Safety and Efficacy of VNS in the Treatment of Mild and Moderate AD Patients; a Multi-center, Randomized, Double-blind, Placebo Parallel Control Trial

This trial will try implanted vagus nerve stimulation versus a sham procedure in people aged 50–80 with mild-to-moderate Alzheimer's to see if it improves thinking, behavior, and daily functioning at six months.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 50 Years to 80 Years
• Sex: All
• Sponsor: Beijing Municipal Administration of Hospitals (Government)
• Locations: 1 site (Beijing)
• Trial ID: NCT06923007 on ClinicalTrials.gov

What this trial studies

This is a randomized, sham-controlled interventional trial comparing active vagus nerve stimulation (VNS) to sham VNS in participants aged 50–80 who meet NIA‑AA criteria for Alzheimer disease with Clinical Dementia Rating scores of 0.5–2. Participants undergo device implantation and are followed with standardized cognitive, neuropsychiatric, and activities-of-daily-living scales, with the primary endpoint being change in ADAS-Cog14 at six months. Secondary outcomes include other cognitive measures, neuropsychiatric symptoms, daily functioning, and safety/tolerability of the device. Study participants must have stable Alzheimer medications and be willing to attend follow-up visits at the study site.

Who should consider this trial

Good fit: Adults aged 50–80 with a clinical NIA‑AA diagnosis of Alzheimer's disease, CDR 0.5–2, on stable Alzheimer medications and willing to undergo device implantation and follow-up are ideal candidates.

Not a fit: People with dementia due to other causes, severe comorbidities, unstable medications, or who cannot undergo implantation or follow-up are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, VNS could improve cognition, reduce neuropsychiatric symptoms, and help people with mild-to-moderate Alzheimer's function better in daily life.

How similar studies have performed: VNS is an established therapy for epilepsy and depression, but prior VNS work in Alzheimer's has been limited and produced mixed or preliminary results, so its benefit in AD is not yet proven.

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.

Where this trial is running

Beijing

• Beijing Tiantan Hospital — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Jianguo Zhang, MD — Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• Study coordinator: Rujin Wang

Conditions Alzheimer Disease; VNS; vagus nerve stimulation