Clinical trial NCT05575271: Implantable Vagus Nerve Stimulation Modulation of Coeruleus-Norepinephrine Network for Mild-Moderate AD Patients
Official title: Implantable Vagus Nerve Stimulation Modulation of Coeruleus-Norepinephrine Network for Mild-Moderate AD Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2022-10-12
Enrollment: 6
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized controlled clinical study will be conducted in Xuanwu Hospital of Capital Medical University. This study initially explore the effect of selective vagus nerve(C fiber) stimulation on mild-to-moderate AD patients, in order to regulate the activity of the locus coeruleus-norepinephrine network, and to observe the improvement of cognitive function and memory function. We aim to evaluate the efficacy and safety of minimally invasive selective vagus nerve stimulation in the treatment of mild-to-moderate AD patients, to clarify the effective mechanism, and to provide an effective clinical treatment strategy.

Detailed description: This project plans to recruit 6 patients with Mild-Moderate Alzheimer's disease. They were randomly divided into vagus nerve active stimulation group and sham stimulation group, to receive vagus nerve stimulator implantation.

2 weeks after implantation, the active group will start the treatment for 12 weeks, and the stimulator of the shame group will be turned off for 12 weeks.

Before treatment, cognitive assessment, head MRI and PET examination of norepinephrine distribution were completed.

Side effects and adverse events were assessed at 6 weeks, 10 weeks, and 14 weeks, and cognitive assessment, head MRI and PET examination of norepinephrine distribution was also performed at the 14th week, Then, the true stimulation group continued to be turned on for 12 weeks, and the sham group turned on the stimulator to start the treatment for 12 weeks. cognitive assessment, head MRI and PET examination of norepinephrine distribution were also performed at 26 weeks.

Eligibility criteria: Inclusion Criteria:

1. Referring to the NIA-AA clinical AD diagnostic criteria formulated by 2011 National Institute on Aging (NIA) and Alzheimer's Disease Association (ADA) groups, select mild to moderate AD patients with positive amyloid PET;
2. Male or female AD patients between the ages of 50-85;
3. Neuropsychological evaluation reaches the following standards: MMSE 16-24 points, CDR 0.5-2 points;
4. Patients who receives a stable cholinesterase inhibitor regimen continues the oral drug with the same dose for at least 8 weeks before entering the study
5. The patient has sufficient proficiency in Mandarin Chinese and is able to complete the cognitive assessment form;
6. Those who voluntarily accept the test and sign an informed consent form.

Exclusion Criteria:

1. There is a clear history of cerebrovascular stroke, and there are clear symptoms or signs of neurological deficit at the time of onset, and there are corresponding responsible lesions left on neuroimaging;
2. Those with a history of alcoholism, or drug addiction, or neurological diseases that can cause cognitive impairment, such as traumatic brain injury, epilepsy, encephalitis, normal intracranial pressure hydrocephalus;
3. Suffering from systemic diseases that may lead to cognitive impairment (such as liver and kidney insufficiency, endocrine diseases, vitamin deficiency);
4. Suffering from cardiac conductive dysfunction (bradycardia) or sleep apnea syndrome;
5. Participating in other drug clinical trials;
6. There are contraindications to head MRI.
7. Those who are deemed unsuitable to participate the trial by the investigator.

Primary outcomes:
measure: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
timeFrame: 26 weeks
Secondary outcomes:
measure: Mini-mental state examination
timeFrame: 26 weeks
measure: Montreal cognitive assessment(MoCA)
timeFrame: 26 weeks
measure: Clinical dementia rating(CDR)
timeFrame: 26 weeks
measure: World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT)
timeFrame: 26 weeks
measure: Digit Span Test
timeFrame: 26 weeks
measure: Trail making test(TMT)
timeFrame: 26 weeks
measure: Boston naming test(BNT)
timeFrame: 26 weeks
measure: Clock-drawing test
timeFrame: 26 weeks
measure: Global Deterioration Scale(GDS)
timeFrame: 26 weeks
measure: Modified hachinski ischemic score
timeFrame: 26 weeks
measure: Neuropsychiatric Inventory(NPI)
timeFrame: 26 weeks
measure: Sturcture MRI
timeFrame: 26 weeks
measure: Functional MRI and Diffussion Tensor Imaging
timeFrame: 26 weeks
measure: Event related potential measured by electroencephalogram
timeFrame: 26 weeks
measure: The norepinephrine transporter PET(NET-PET)
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University.
Study officials:
References: