Back to resultsImplantable Vagus Nerve Stimulation Modulation of Coeruleus-Norepinephrine Network for Mild-Moderate AD Patients
Primary Purpose
Alzheimer Disease
Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Xuanwu Hospital, Capital Medical University.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Vagus nerve stimulation
Sham stimulation
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
To evaluate the improvement of the cognitive state of AD patients
Secondary Outcome Measures
Mini-mental state examination
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.
Montreal cognitive assessment(MoCA)
To evaluate the improvement of the cognitive state of AD patients
Clinical dementia rating(CDR)
To evaluate the improvement of the cognitive state of AD patients
World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT)
To evaluate the improvement of the cognitive state of AD patients
Digit Span Test
To evaluate the improvement of the cognitive state of AD patients
Trail making test(TMT)
To evaluate the improvement of the cognitive state of AD patients
Boston naming test(BNT)
To evaluate the improvement of the cognitive state of AD patients
Clock-drawing test
To evaluate the improvement of the cognitive state of AD patients
Global Deterioration Scale(GDS)
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.
Modified hachinski ischemic score
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.
Neuropsychiatric Inventory(NPI)
To assess the improvement of common behaviors associated with dementia
Sturcture MRI
To evaluate the morphologic change of locus coeruleus
Functional MRI and Diffussion Tensor Imaging
To evaluate the brain connectivity change
Event related potential measured by electroencephalogram
To evaluate the improvement of the working memory
The norepinephrine transporter PET(NET-PET)
To evaluate the change of norepinephrine distribution of the brain
Full Information
NCT ID
NCT05575271
First Posted
July 14, 2022
Last Updated
October 9, 2022
Sponsor
Xuanwu Hospital, Beijing
1. Study Identification
Unique Protocol Identification Number
NCT05575271
Brief Title
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
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2022 (Anticipated)
Primary Completion Date
September 1, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xuanwu Hospital, Beijing
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vagus nerve stimulation
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network
Intervention Description
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.
Primary Outcome Measure Information:
Title
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Mini-mental state examination
Description
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.
Time Frame
26 weeks
Title
Montreal cognitive assessment(MoCA)
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Title
Clinical dementia rating(CDR)
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Title
World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT)
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Title
Digit Span Test
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Title
Trail making test(TMT)
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Title
Boston naming test(BNT)
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Title
Clock-drawing test
Description
To evaluate the improvement of the cognitive state of AD patients
Time Frame
26 weeks
Title
Global Deterioration Scale(GDS)
Description
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.
Time Frame
26 weeks
Title
Modified hachinski ischemic score
Description
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.
Time Frame
26 weeks
Title
Neuropsychiatric Inventory(NPI)
Description
To assess the improvement of common behaviors associated with dementia
Time Frame
26 weeks
Title
Sturcture MRI
Description
To evaluate the morphologic change of locus coeruleus
Time Frame
26 weeks
Title
Functional MRI and Diffussion Tensor Imaging
Description
To evaluate the brain connectivity change
Time Frame
26 weeks
Title
Event related potential measured by electroencephalogram
Description
To evaluate the improvement of the working memory
Time Frame
26 weeks
Title
The norepinephrine transporter PET(NET-PET)
Description
To evaluate the change of norepinephrine distribution of the brain
Time Frame
26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guoguang Zhao, M.D.
Phone
13701294528
Email
ggzhao@vip.sina.com
Facility Information:
Facility Name
Xuanwu Hospital, Capital Medical University.
City
Beijing
ZIP/Postal Code
100053
Country
China
12. IPD Sharing Statement
Learn more about this trial
Implantable Vagus Nerve Stimulation Modulation of Coeruleus-Norepinephrine Network for Mild-Moderate AD Patients
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