Alzheimer DiseaseNCT05575271
Implantable Vagus Nerve Stimulation Modulation of Coeruleus-Norepinephrine Network for Mild-Moderate AD Patients
A study testing Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network in people with Alzheimer Disease, run by Xuanwu Hospital, Beijing at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2022to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the 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
- Being tested
- Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine NetworkProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Vagus nerve stimulation | Experimental | 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. Receives: Procedure: Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network |
| Sham stimulation | Sham comparator | 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. Receives: Procedure: Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
To evaluate the improvement of the cognitive state of AD patients
Measured: 26 weeks
Secondary outcomes (15)
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.
Measured: 26 weeks
Montreal cognitive assessment(MoCA)
To evaluate the improvement of the cognitive state of AD patients
Measured: 26 weeks
Clinical dementia rating(CDR)
To evaluate the improvement of the cognitive state of AD patients
Measured: 26 weeks
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
Measured: 26 weeks
Digit Span Test
To evaluate the improvement of the cognitive state of AD patients
Measured: 26 weeks
Trail making test(TMT)
To evaluate the improvement of the cognitive state of AD patients
Measured: 26 weeks
Boston naming test(BNT)
To evaluate the improvement of the cognitive state of AD patients
Measured: 26 weeks
Clock-drawing test
To evaluate the improvement of the cognitive state of AD patients
Measured: 26 weeks
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.
Measured: 26 weeks
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.
Measured: 26 weeks
Neuropsychiatric Inventory(NPI)
To assess the improvement of common behaviors associated with dementia
Measured: 26 weeks
Sturcture MRI
To evaluate the morphologic change of locus coeruleus
Measured: 26 weeks
Functional MRI and Diffussion Tensor Imaging
To evaluate the brain connectivity change
Measured: 26 weeks
Event related potential measured by electroencephalogram
To evaluate the improvement of the working memory
Measured: 26 weeks
The norepinephrine transporter PET(NET-PET)
To evaluate the change of norepinephrine distribution of the brain
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2022
- Study start1 Nov 2022 (estimated)
- Primary completion1 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Xuanwu Hospital, BeijingThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanwu Hospital, Beijing
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05575271
- Sponsor's protocol ID
- XW-[2022]110-AD/VNS
- Status last verified
- Oct 2022
- First submitted
- 14 Jul 2022
- Last updated
- 12 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implantable Vagus Nerve Stimulation Modulation of Coeruleus-Norepinephrine Network for Mild-Moderate AD Patients
- ClinicalTrials.gov ID
- NCT05575271
- Acronym / sponsor ID
- XW-[2022]110-AD/VNS
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Xuanwu Hospital, BeijingUniversity, hospital or other
- Study start
- 1 Nov 2022 (estimated)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 12 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vagus nerve stimulation | Experimental | Procedure: Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine NetworkThe 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. |
| Sham stimulation | Sham comparator | Procedure: Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network2 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. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine NetworkThe 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. | Procedure or surgery | Sham stimulation, Vagus nerve stimulation |
Primary outcome
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Time frame: 26 weeks
To evaluate the improvement of the cognitive state of AD patients
15 secondary outcomes
Mini-mental state examination
Time frame: 26 weeks
Montreal cognitive assessment(MoCA)
Time frame: 26 weeks
Clinical dementia rating(CDR)
Time frame: 26 weeks
World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT)
Time frame: 26 weeks
Digit Span Test
Time frame: 26 weeks
Trail making test(TMT)
Time frame: 26 weeks
Boston naming test(BNT)
Time frame: 26 weeks
Clock-drawing test
Time frame: 26 weeks
Global Deterioration Scale(GDS)
Time frame: 26 weeks
Modified hachinski ischemic score
Time frame: 26 weeks
Neuropsychiatric Inventory(NPI)
Time frame: 26 weeks
Sturcture MRI
Time frame: 26 weeks
Functional MRI and Diffussion Tensor Imaging
Time frame: 26 weeks
Event related potential measured by electroencephalogram
Time frame: 26 weeks
The norepinephrine transporter PET(NET-PET)
Time frame: 26 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vagus Nerve Stimulation Modulation of the Coeruleus-Norepinephrine Network in people with Alzheimer Disease, run by Xuanwu Hospital, Beijing at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guoguang Zhao, M.D. (13701294528, ggzhao@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022; AzTrials last refreshed its copy on 6 Nov 2026.