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

October 9, 2022 updated by: Xuanwu Hospital, Beijing
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
      • Beijing, China, 100053
        • Xuanwu Hospital, Capital Medical University.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Procedure: 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.
Sham Comparator: 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.
Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mini-mental state examination
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients. The scale consists of 20 questions with a total of 30 items, involving five aspects of orientation, memory, attention and calculation, recall, and language. It can be used as a screening examination and evaluation method for patients with moderate or severe dementia.
26 weeks
Montreal cognitive assessment(MoCA)
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks
Clinical dementia rating(CDR)
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks
World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT)
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks
Digit Span Test
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks
Trail making test(TMT)
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks
Boston naming test(BNT)
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks
Clock-drawing test
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
26 weeks
Global Deterioration Scale(GDS)
Time Frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients.The Global Deterioration Scale (GDS), developed by Dr. Barry Reisberg, provides caregivers an overview of the stages of cognitive function for those suffering from a primary degenerative dementia such as Alzheimer's disease. It is broken down into 7 different stages. Stages 1-3 are the pre-dementia stages. Stages 4-7 are the dementia stages. Biginning in stage 5, an individual can no longer survive without assistance.
26 weeks
Modified hachinski ischemic score
Time Frame: 26 weeks
The modified Hachinski ischaemic scale is an attempt to differentiate Alzheimer's type dementia and multi-infarct dementia.A score of 2 or less are typical of a patient with Alzheimer's disease. A score of greater than 2 is typical of multi-infarct dementia.
26 weeks
Neuropsychiatric Inventory(NPI)
Time Frame: 26 weeks
To assess the improvement of common behaviors associated with dementia
26 weeks
Sturcture MRI
Time Frame: 26 weeks
To evaluate the morphologic change of locus coeruleus
26 weeks
Functional MRI and Diffussion Tensor Imaging
Time Frame: 26 weeks
To evaluate the brain connectivity change
26 weeks
Event related potential measured by electroencephalogram
Time Frame: 26 weeks
To evaluate the improvement of the working memory
26 weeks
The norepinephrine transporter PET(NET-PET)
Time Frame: 26 weeks
To evaluate the change of norepinephrine distribution of the brain
26 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xuanwu Hospital, Beijing

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 14, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • XW-[2022]110-AD/VNS

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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