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

NCT ID: NCT05575271

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2026-12-31

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.

Conditions

Alzheimer Disease

Study Design

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

Study Groups

Vagus nerve stimulation

The stimulator will be activated 2 weeks after the operation and continue for 24 weeks. The initial parameters of the program is set as: current 0.20mA, pulse width 500us, frequency 20Hz, stimulation time 30s, interval time 5min. A dynamic program control will be started at a speed of 0.20 mA, and the stimulation intensity will be controlled with the range of 0.4- 0.8mA.

Group Type: EXPERIMENTAL

Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network

Intervention Type: PROCEDURE

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.

Sham stimulation

2 weeks after the operation, the stimulator will be turned off for 12 weeks. Then the stimulator will be turned on for 12 weeks. The initial parameters of the program is set as: current 0.20mA, pulse width 500us, frequency 20Hz, stimulation time 30s, interval time 5min. A dynamic program control will be started at a speed of 0.20 mA, and the stimulation intensity will be controlled with the range of 0.4- 0.8mA.

Group Type: SHAM_COMPARATOR

Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Xuanwu Hospital, Capital Medical University.

Beijing, , China

Countries

China

Central Contacts

Guoguang Zhao, M.D.

Role: CONTACT

ggzhao@vip.sina.com

13701294528

Other Identifiers

XW-[2022]110-AD/VNS

Identifier Type: -

Identifier Source: org_study_id