Mild Cognitive ImpairmentNCT05514756
VINCI-AD: An Investigation of Transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment.
A study testing Active t-VNS and Baseline assessments in people with Mild Cognitive Impairment and Neurocardiogenic Syncope, run by Tallaght University Hospital at 1 site in Ireland.
Trial summary
The VINCI-AD study will investigate the impact of non-invasive vagus nerve stimulation (VNS) on memory in participants with existing mild memory impairment. VNS is a safe, existing treatment, licensed in epilepsy and depression. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Mild Cognitive Impairment, Neurocardiogenic Syncope, Memory Impairment
- What is being tested?
- Active t-VNS and Baseline assessments
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteIreland
- Study dates
- 1 Jun 2022to 30 Jun 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Mild Cognitive Impairment as defined by Clinical Dementia Rating Scale Global score of 0.5
- one RBANS index indicating multi-domain amnestic MCI, amnestic MCI or non-amnestic MCI
- native English speakers
Who cannot join
- significant current depression
- uncorrected vision/hearing loss
- history of brain surgery
- history of epilepsy with seizure event in last year
- taking any pharmacological agents known to significantly increase seizure risk
- arrhythmia including atrial fibrillation
Show all 10Show fewer
- pacemaker implants
- existing left ear deformity or recent ear trauma
- alcohol dependence
- currently taking DMARDs or immunotherapies
Trial locations and contacts
1 site in 1 country.
About this study
Official title: VINCI-AD: An Investigation of Transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment
The VINCI-AD study will investigate the impact of non-invasive vagus nerve stimulation (VNS) on memory in participants with existing mild memory impairment. VNS is a safe, existing treatment, licensed in epilepsy and depression. Until recently, stimulating the vagus nerve involved an operation (invasive VNS) but we can now perform VNS by stimulating a nerve in the outer ear with a very gentle current using a small earpiece, called transcutaneous vagus nerve stimulation (t-VNS). Previous studies have indicated that invasive VNS may improve memory in people with no cognitive issues or with dementia. No study has examined the use of t-VNS in people with diagnosed mild memory issues. The main aim of this study is to assess the feasibility of using t-VNS in participants with Mild Cognitive Impairment (MCI). Other objectives include: 1) Determining the optimal stimulation settings to improve memory; 2) Assessment of safety and tolerability of VNS in participants with memory impairment ; 3) Exploration of impact of non-invasive VNS on brain oxygenation via near-infrared spectroscopy (NIRS): 4) Assessment of impact of VNS on blood markers of inflammation: 5) Assessment of impact of VNS on heart rate variability (HRV) and orthostatic stress in participants with memory impairment. The study will enroll participants via the memory assessment service who have been diagnosed with MCI. The study will enroll 40 participants. All eligible participants will undergo three assessments; one as a baseline assessment of neurocardiovascular health, baseline cognitive tests and baseline blood tests. They will then return for two further visits, one while undergoing active stimulation (active t-VNS) and one while undergoing sham stimulation (sham t-VNS).
Read the detailed description
The VINCI-AD study is an investigator-led, single-centre crossover device study of the NEMOS Cerbomed auricular transcutaneous vagus nerve stimulator (t-VNS) device in participants with diagnosed Mild Cognitive Impairment (MCI). The study will assess the feasibility, safety and tolerability of the study device for the treatment of older adults with MCI. The device contains a small electrode programmed to 8 Hz stimulation, with participant-selected amplitude settings, which delivers a small amount of stimulation to the vagus nerve via the auricular branch of the vagus nerve located in the outer ear. All eligible participants will be enrolled to three visits to the investigation site, wherein they will undergo baseline (no stimulation), active or sham stimulation for 60 minutes during assessments. Participants will act as their own controls with baseline and sham assessments, undertaken 7-10 days apart. The study is single-blinded as the participants will not be aware whether active or sham stimulation is ongoing during respective assessments.
Neurocardiovascular assessments will be initially undertaken at each visit, encompassing heart rate variability (HRV) measures, active stand after minimum of 5 minutes lying supine, with associated near-infrared spectroscopy (NIRS) assessments. Given the orthostatic challenge, each participant will be asked to not consume caffeine prior to assessment and to attend at 14:00 for each assessment. Orthostatic challenges are undertaken indoors at 21 degrees centigrade in the research laboratory.
Cognitive tests undertaken will encompass a computer-based associative memory task, involving 30 Face-Name association pairs; the Sustained Attention Response to Task (SART) test, spatial navigation via Sea Hero Quest Research App and Repeatable Battery for Assessment of Neuropsychological Status examination. NIRS assessment will be ongoing during cognitive testing.
Serum and plasma markers of inflammation including cytokines and chemokines will be taken after each assessment (baseline, active and sham stimulation).
- Conditions
- Mild Cognitive Impairment, Neurocardiogenic Syncope, Memory Impairment, Inflammatory Response, Alzheimer Disease
- Being tested
- Active t-VNS, Sham t-VNS, Baseline assessments
- Medical subject headings
- Cognitive Dysfunction, Syncope, Vasovagal, Memory Disorders, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active t-VNSDevice
Active t-VNS at 8 Hz for up to 60 minutes will be applied to the left cymba conchae
Sham t-VNSDevice
Sham t-VNS at 8 Hz for up to 60 minutes will be applied to the left earlobe
Baseline assessmentsOther
Baselines assessments with no stimulation will serve as control in this three-part crossover design
| Study group | Role | What they receive |
|---|---|---|
| Active t-VNS | Active comparator | Active t-VNS at 8 Hz to the left cymba conchae, acutely for up to 60 minutes Receives: Device: Active t-VNS |
| Sham t-VNS | Sham comparator | Sham t-VNS at 8 Hz to the left earlobe, acutely for up to 60 minutes Receives: Device: Sham t-VNS |
| Baseline assessments | Placebo comparator | Baseline assessments of neurocardiovascular stability, cognition and serum and plasma inflammatory markers per participant serve to act as their own control in this three-part crossover design Receives: Other: Baseline assessments |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of acute t-VNS in participants with MCI - assessed via orthostatic challenge
Orthostatic stress is measured via the active stand test whereby participants lie supine for 5 minutes with beat to beat blood pressure (BP) monitoring. They then stand and BP response to orthostatic challenge is measured. To standardise assessments, they are all taken at 14:00 each day, without nicotine or caffeine consumed that day, and all routine meds are taken as usual each morning. Orthostatic hypotension is defined by consensus as a sustained reduction of systolic blood pressure (SBP) of at least 20 mmHg or diastolic blood pressure (DBP) of 10 mmHg within 3 minutes of standing
Measured: acute (less than 60 minutes)
Safety of acute t-VNS in participants with MCI - assessed via structured assessments of adverse events (AEs) and serious adverse events (SAEs)
Likert based questionnaires have been developed to assess for the routine side effects noted in the literature for acute t-VNS treatment including pain, skin discomfort, tingling, headache, tinnitus. These Likert scales are rated 1 to 5 with 1 = worse symptoms and 5 = no symptoms, and will be undertaken after active and sham stimulation. Participants will be given contact details of the principal investigator and study coordinator at the hospital who they can contact if they have concerns or any new symptoms arise.
Measured: acute (less than 60 minutes)
Tolerability of acute t-VNS in participants with MCI
Tolerability of the device will be assessed via in-person questionnaires involving Likert-based scales rated 1 to 5 with 1 = poorly tolerable / painful and 5 = no discomfort noted / comfortable
Measured: acute (less than 60 minutes)
Secondary outcomes (6)
Effect of acute t-VNS on associative memory in participants with MCI
The Face Name Association Test is a cross-modal associative memory test involving Face-Name pairs, of which the participant is shown 30 pairs and then asked to recall if they have been shown before, and if so what their name was. t-VNS has been shown to boost associative memory as assessed by this task in cognitively unimpaired older adults, but has not been assessed in those with MCI. Near-infrared spectroscopy (NIRS) assessment will be ongoing during cognitive assessments, and the assessments will be undertaken 3 times, once at baseline, once during sham once during active t-VNS with 7-10 days between assessments
Measured: acute (less than 60 minutes)
Effect of acute t-VNS on inhibitory control in participants with MCI
The Sustained Attention to Response Task (SART) is a computer-based go/no-go task that requires participants to withhold behavioral response to a single, infrequent target (often the digit 3) presented amongst a background of frequent non-targets (0-2, 4-9). There is evidence supporting the role of the SART as a measure of working memory, sustained attention, and impulse/inhibitory control. We will measure participants' response times and accuracy, at baseline, during active and sham t-VNS with near infrared spectroscopy (NIRS) measurements ongoing during task.
Measured: acute (less than 60 minutes)
Effect of acute t-VNS on spatial navigation in participants with MCI
Sea Hero Quest is a multi-platform mobile game designed to help advance the understanding of spatial navigation and 3D navigation, which is one of the first skills lost in dementia. We will measure participants' ability to navigate through 5 pre-specified levels of Sea Hero Quest, specifically speed and accuracy of navigation. Near-infrared specroscopy (NIRS) measurement will be ongoing during assessment and the assessments will be undertaken at baseline, during active and sham t-VNS.
Measured: acute (less than 60 minutes)
Effect of acute t-VNS on heart rate variability in participants with MCI
Heart rate variability (HRV) is an index of the beat- to beat variability between heart beats. Increased vagal tone (and thus vagal action) is generally associated with a lower heart rate and increased HRV. Indices of HRV including SDNN, RMSSD, HF/LF ratio will be obtained during 5 minutes of rest pre -orthostatic stress. Baseline HRV, and HRV during both active t-VNS and sham t-VNS will be obtained for each participant
Measured: acute (less than 60 minutes)
Effect of acute t-VNS on serum and plasma chemokines and cytokines in participants with MCI
Non-invasive VNS has been shown to downregulate inflammatory cytokine release in healthy young participants, but has not been assessed in participants with MCI. We aim to measure a wide array of blood based cytokines and chemokines using the Luminex assay. Serum and plasma samples will be taken at baseline assessment, after acute active t-VNS and sham t-VNS.
Measured: acute (less than 60 minutes)
Utility of t-VNS device in participants with MCI
Participants' objective ability to utilise and troubleshot the t-VNS device will be assessed via modified Kettle test; a brief Occupational Therapy performance-based measure designed to assess cognitive skills in a functional context.
Measured: acute (less than 60 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2022
- Study start1 Jun 2022
- Primary completion30 Jun 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- 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
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tallaght University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sean P Kennelly, Tallaght University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05514756
- Sponsor's protocol ID
- VINCI-AD
- Status last verified
- Jun 2024
- First submitted
- 29 Jul 2022
- Last updated
- 14 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share individual patient data with other researchers
Publications
Dolphin H, Dyer AH, Dukelow T, Finucane C, Commins S, Kennelly SP. Safety and feasibility of transcutaneous vagus nerve stimulation in mild cognitive impairment: VINCI-AD study protocol. BMC Neurol. 2023 Aug 2;23(1):289. doi: 10.1186/s12883-023-03320-5.
PubMed 37532979
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VINCI-AD: An Investigation of Transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT05514756
- Acronym / sponsor ID
- VINCI-AD
- Conditions
- Mild Cognitive Impairment, Neurocardiogenic Syncope, Memory Impairment, Inflammatory Response, Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Tallaght University HospitalUniversity, hospital or other
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 24 Aug 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.
The VINCI-AD study will investigate the impact of non-invasive vagus nerve stimulation (VNS) on memory in participants with existing mild memory impairment. VNS is a safe, existing treatment, licensed in epilepsy and depression. Until recently, stimulating the vagus nerve involved an operation (invasive VNS) but we can now perform VNS by stimulating a nerve in the outer ear with a very gentle current using a small earpiece, called transcutaneous vagus nerve stimulation (t-VNS). Previous studies have indicated that invasive VNS may improve memory in people with no cognitive issues or with dementia. No study has examined the use of t-VNS in people with diagnosed mild memory issues. The main aim of this study is to assess the feasibility of using t-VNS in participants with Mild Cognitive Impairment (MCI). Other objectives include: 1) Determining the optimal stimulation settings to improve memory; 2) Assessment of safety and tolerability of VNS in participants with memory impairment ; 3) Exploration of impact of non-invasive VNS on brain oxygenation via near-infrared spectroscopy (NIRS): 4) Assessment of impact of VNS on blood markers of inflammation: 5) Assessment of impact of VNS on heart rate variability (HRV) and orthostatic stress in participants with memory impairment. The study will enroll participants via the memory assessment service who have been diagnosed with MCI. The study will enroll 40 participants. All eligible participants will undergo three assessments; one as a baseline assessment of neurocardiovascular health, baseline cognitive tests and baseline blood tests. They will then return for two further visits, one while undergoing active stimulation (active t-VNS) and one while undergoing sham stimulation (sham t-VNS).
Detailed description
The VINCI-AD study is an investigator-led, single-centre crossover device study of the NEMOS Cerbomed auricular transcutaneous vagus nerve stimulator (t-VNS) device in participants with diagnosed Mild Cognitive Impairment (MCI). The study will assess the feasibility, safety and tolerability of the study device for the treatment of older adults with MCI. The device contains a small electrode programmed to 8 Hz stimulation, with participant-selected amplitude settings, which delivers a small amount of stimulation to the vagus nerve via the auricular branch of the vagus nerve located in the outer ear. All eligible participants will be enrolled to three visits to the investigation site, wherein they will undergo baseline (no stimulation), active or sham stimulation for 60 minutes during assessments. Participants will act as their own controls with baseline and sham assessments, undertaken 7-10 days apart. The study is single-blinded as the participants will not be aware whether active or sham stimulation is ongoing during respective assessments.
Neurocardiovascular assessments will be initially undertaken at each visit, encompassing heart rate variability (HRV) measures, active stand after minimum of 5 minutes lying supine, with associated near-infrared spectroscopy (NIRS) assessments. Given the orthostatic challenge, each participant will be asked to not consume caffeine prior to assessment and to attend at 14:00 for each assessment. Orthostatic challenges are undertaken indoors at 21 degrees centigrade in the research laboratory.
Cognitive tests undertaken will encompass a computer-based associative memory task, involving 30 Face-Name association pairs; the Sustained Attention Response to Task (SART) test, spatial navigation via Sea Hero Quest Research App and Repeatable Battery for Assessment of Neuropsychological Status examination. NIRS assessment will be ongoing during cognitive testing.
Serum and plasma markers of inflammation including cytokines and chemokines will be taken after each assessment (baseline, active and sham stimulation).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active t-VNS | Active comparator | Device: Active t-VNSActive t-VNS at 8 Hz to the left cymba conchae, acutely for up to 60 minutes |
| Sham t-VNS | Sham comparator | Device: Sham t-VNSSham t-VNS at 8 Hz to the left earlobe, acutely for up to 60 minutes |
| Baseline assessments | Placebo comparator | Other: Baseline assessmentsBaseline assessments of neurocardiovascular stability, cognition and serum and plasma inflammatory markers per participant serve to act as their own control in this three-part crossover design |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Mild Cognitive Impairment as defined by Clinical Dementia Rating Scale Global score of 0.5
- one RBANS index indicating multi-domain amnestic MCI, amnestic MCI or non-amnestic MCI
- native English speakers
Key exclusion criteria (10 listed)
- significant current depression
- uncorrected vision/hearing loss
- history of brain surgery
- history of epilepsy with seizure event in last year
- taking any pharmacological agents known to significantly increase seizure risk
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 |
|---|---|---|
| Active t-VNSActive t-VNS at 8 Hz for up to 60 minutes will be applied to the left cymba conchae | Device | Active t-VNS |
| Sham t-VNSSham t-VNS at 8 Hz for up to 60 minutes will be applied to the left earlobe | Device | Sham t-VNS |
| Baseline assessmentsBaselines assessments with no stimulation will serve as control in this three-part crossover design | Other | Baseline assessments |
Primary outcome
Safety of acute t-VNS in participants with MCI - assessed via orthostatic challenge
Time frame: acute (less than 60 minutes)
Orthostatic stress is measured via the active stand test whereby participants lie supine for 5 minutes with beat to beat blood pressure (BP) monitoring. They then stand and BP response to orthostatic challenge is measured. To standardise assessments, they are all taken at 14:00 each day, without nicotine or caffeine consumed that day, and all routine meds are taken as usual each morning. Orthostatic hypotension is defined by consensus as a sustained reduction of systolic blood pressure (SBP) of at least 20 mmHg or diastolic blood pressure (DBP) of 10 mmHg within 3 minutes of standing
Safety of acute t-VNS in participants with MCI - assessed via structured assessments of adverse events (AEs) and serious adverse events (SAEs)
Time frame: acute (less than 60 minutes)
Likert based questionnaires have been developed to assess for the routine side effects noted in the literature for acute t-VNS treatment including pain, skin discomfort, tingling, headache, tinnitus. These Likert scales are rated 1 to 5 with 1 = worse symptoms and 5 = no symptoms, and will be undertaken after active and sham stimulation. Participants will be given contact details of the principal investigator and study coordinator at the hospital who they can contact if they have concerns or any new symptoms arise.
Tolerability of acute t-VNS in participants with MCI
Time frame: acute (less than 60 minutes)
Tolerability of the device will be assessed via in-person questionnaires involving Likert-based scales rated 1 to 5 with 1 = poorly tolerable / painful and 5 = no discomfort noted / comfortable
6 secondary outcomes
Effect of acute t-VNS on associative memory in participants with MCI
Time frame: acute (less than 60 minutes)
Effect of acute t-VNS on inhibitory control in participants with MCI
Time frame: acute (less than 60 minutes)
Effect of acute t-VNS on spatial navigation in participants with MCI
Time frame: acute (less than 60 minutes)
Effect of acute t-VNS on heart rate variability in participants with MCI
Time frame: acute (less than 60 minutes)
Effect of acute t-VNS on serum and plasma chemokines and cytokines in participants with MCI
Time frame: acute (less than 60 minutes)
Utility of t-VNS device in participants with MCI
Time frame: acute (less than 60 minutes)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Derived from this study: PubMed 37532979Dolphin H, Dyer AH, Dukelow T, Finucane C, Commins S, Kennelly SP. Safety and feasibility of transcutaneous vagus nerve stimulation in mild cognitive impairment: VINCI-AD study protocol. BMC Neurol. 2023 Aug 2;23(1):289. doi: 10.1186/s12883-023-03320-5.
- Individual participant dataSharing planned: No. There is no plan to share individual patient data with other researchers
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active t-VNS and Baseline assessments in people with Mild Cognitive Impairment and Neurocardiogenic Syncope, run by Tallaght University Hospital at 1 site in Ireland.
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 3 inclusion and 10 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: finished, as of the sponsor's last update on 14 Jun 2024. 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 Ireland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of acute t-VNS in participants with MCI - assessed via orthostatic challenge (time frame: acute (less than 60 minutes)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05514756, which also lists 1 linked publication.
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 14 Jun 2024.