VINCI-AD: An Investigation of Transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment.
Study Details
Study Description
Brief 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. 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 60 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
The VINCI-AD study is an investigator-led, single-centre crossover device trial 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 or 25 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 labortaory.
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Active t-VNS Active t-VNS at 8 Hz to the left cymba conchae, acutely for up to 60 minutes |
Device: Active t-VNS
Active t-VNS at 8 Hz for up to 60 minutes will be applied to the left cymba conchae
|
| Sham Comparator: Sham t-VNS Sham t-VNS at 8 Hz to the left earlobe, acutely for up to 60 minutes |
Device: Sham t-VNS
Sham t-VNS at 8 Hz for up to 60 minutes will be applied to the left earlobe
|
| Placebo Comparator: Baseline assessments 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 |
Other: Baseline assessments
Baselines assessments with no stimulation will serve as control in this three-part crossover design
|
Outcome Measures
Primary Outcome Measures
- Effect of acute t-VNS on associative memory in participants with MCI [acute (less than 60 minutes)]
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
Secondary Outcome Measures
- Effect of acute t-VNS on orthostatic challenge in participants with MCI [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. Abnormal orthostatic BP responses can be defined as initial orthostatic hypotension (a transient systolic BP fall of >40 mmHg within 15 s of standing), delayed BP recovery (an inability of systolic BP to recover to a value of >20 mmHg below baseline at 30 s after standing) and sustained orthostatic hypotension (a sustained decline in systolic BP of ≥20 mmHg occurring 60-180 s after standing).
- Effect of acute t-VNS on heart rate variability in participants with MCI [acute (less than 60 minutes)]
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
- Effect of acute t-VNS on inhibitory control in participants with MCI [acute (less than 60 minutes)]
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.
- Effect of acute t-VNS on spatial navigation in participants with MCI [acute (less than 60 minutes)]
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.
- Effect of acute t-VNS on serum and plasma chemokines and cytokines in participants with MCI [acute (less than 60 minutes)]
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.
- Acceptability of t-VNS device in participants with MCI [acute (less than 60 minutes)]
Acceptability of the device will be assessed via in-person questionnaires involving Likert-based scales.
- Utility of t-VNS device in participants with MCI [acute (less than 60 minutes)]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Mild Cognitive Impairment as defined by Clinical Dementia Rating Scale Global score of 0.5
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one RBANS index indicating multi-domain amnestic MCI, amnestic MCI or non-amnestic MCI
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native English speakers
Exclusion Criteria:
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significant current depression
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uncorrected vision/hearing loss
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history of brain surgery
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history of epilepsy with seizure event in last year
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taking any pharmacological agents known to significantly increase seizure risk
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arrhythmia including atrial fibrillation
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pacemaker implants
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existing left ear deformity or recent ear trauma
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alcohol dependence
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currently taking DMARDs or immunotherapies
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tallaght University Hospital | Dublin | Ireland | D24NR04 |
Sponsors and Collaborators
- Tallaght University Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VINCI-AD