Clinical trial NCT05514756: VINCI-AD: An Investigation of Transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment.
Official title: VINCI-AD: An Investigation of Transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Cognitive Impairment
Neurocardiogenic Syncope
Memory Impairment
Inflammatory Response
Alzheimer Disease
Lead sponsor: Tallaght University Hospital
Sponsor class: OTHER
First posted: 2022-08-24
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* pacemaker implants
* existing left ear deformity or recent ear trauma
* alcohol dependence
* currently taking DMARDs or immunotherapies

Primary outcomes:
measure: Safety of acute t-VNS in participants with MCI - assessed via orthostatic challenge
timeFrame: acute (less than 60 minutes)
measure: Safety of acute t-VNS in participants with MCI - assessed via structured assessments of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: acute (less than 60 minutes)
measure: Tolerability of acute t-VNS in participants with MCI
timeFrame: acute (less than 60 minutes)
Secondary outcomes:
measure: Effect of acute t-VNS on associative memory in participants with MCI
timeFrame: acute (less than 60 minutes)
measure: Effect of acute t-VNS on inhibitory control in participants with MCI
timeFrame: acute (less than 60 minutes)
measure: Effect of acute t-VNS on spatial navigation in participants with MCI
timeFrame: acute (less than 60 minutes)
measure: Effect of acute t-VNS on heart rate variability in participants with MCI
timeFrame: acute (less than 60 minutes)
measure: Effect of acute t-VNS on serum and plasma chemokines and cytokines in participants with MCI
timeFrame: acute (less than 60 minutes)
measure: Utility of t-VNS device in participants with MCI
timeFrame: acute (less than 60 minutes)
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Tallaght University Hospital
Study officials:
References: