Implantable Vagus Nerve Stimulation Modulation of Coeruleus-Norepinephrine Network for Mild-Moderate AD Patients

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network
  The implant surgery is performed under general anesthesia. The generator is implanted subcutaneously in the left upper chest or left axillary border. The electrode lead wire is attached to the left mid-cervical vagus nerve through a second incision in the left neck area. The lead wire is passed through a subcutaneous tunnel and attached to the pulse generator.

Первичные конечные точки

• Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) [Срок оценки: 26 weeks]

Вторичные конечные точки (12)

• Mini-mental state examination [Срок оценки: 26 weeks]
• Montreal cognitive assessment(MoCA) [Срок оценки: 26 weeks]
• Clinical dementia rating(CDR) [Срок оценки: 26 weeks]
• World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) [Срок оценки: 26 weeks]
• Digit Span Test [Срок оценки: 26 weeks]
• Trail making test(TMT) [Срок оценки: 26 weeks]
• Boston naming test(BNT) [Срок оценки: 26 weeks]
• Clock-drawing test [Срок оценки: 26 weeks]
• Global Deterioration Scale(GDS) [Срок оценки: 26 weeks]
• Modified hachinski ischemic score [Срок оценки: 26 weeks]
• Neuropsychiatric Inventory(NPI) [Срок оценки: 26 weeks]
• Sturcture MRI [Срок оценки: 26 weeks]

Критерии участия

Критерии включения

• 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;
• Male or female AD patients between the ages of 50-85;
• Neuropsychological evaluation reaches the following standards: MMSE 16-24 points, CDR 0.5-2 points;
• 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
• The patient has sufficient proficiency in Mandarin Chinese and is able to complete the cognitive assessment form;
• Those who voluntarily accept the test and sign an informed consent form.

Критерии исключения

• 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;
• 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;
• Suffering from systemic diseases that may lead to cognitive impairment (such as liver and kidney insufficiency, endocrine diseases, vitamin deficiency);
• Suffering from cardiac conductive dysfunction (bradycardia) or sleep apnea syndrome;
• Participating in other drug clinical trials;
• There are contraindications to head MRI.
• Those who are deemed unsuitable to participate the trial by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Xuanwu Hospital, Capital Medical University. — Пекин

Идентификаторы

NCT: NCT05575271 · XW-[2022]110-AD/VNS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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