VINCI-AD: An Investigation of Transcutaneous Vagus Nerve Stimulation in Mild Cognitive Impairment.

NCT05514756 | Completed

• 1 other identifier: VINCI-AD
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Mild Cognitive Impairment; Neurocardiogenic Syncope; Memory Impairment; Inflammatory Response; Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• 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

  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.

  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

  acute (less than 60 minutes)

Secondary Outcomes (6)

• Effect of acute t-VNS on associative memory in participants with MCI

  acute (less than 60 minutes)

• Effect of acute t-VNS on inhibitory control in participants with MCI

  acute (less than 60 minutes)

• Effect of acute t-VNS on spatial navigation in participants with MCI

  acute (less than 60 minutes)

• Effect of acute t-VNS on heart rate variability in participants with MCI

  acute (less than 60 minutes)

• Effect of acute t-VNS on serum and plasma chemokines and cytokines in participants with MCI

  acute (less than 60 minutes)

Study Arms (3)

Active t-VNS

ACTIVE COMPARATOR

Active t-VNS at 8 Hz to the left cymba conchae, acutely for up to 60 minutes

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

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

Other: Baseline assessments

Interventions

Active t-VNS DEVICE

Active t-VNS at 8 Hz for up to 60 minutes will be applied to the left cymba conchae

Active t-VNS

Sham t-VNS DEVICE

Sham t-VNS at 8 Hz for up to 60 minutes will be applied to the left earlobe

Sham t-VNS

Baseline assessments OTHER

Baselines assessments with no stimulation will serve as control in this three-part crossover design

Baseline assessments

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tallaght University Hospital: lead

Study Sites (1)

Tallaght University Hospital

Dublin, D24NR04, Ireland

Location

Related Publications (1)

• 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.

  PMID: 37532979 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Syncope, Vasovagal; Memory Disorders; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Syncope; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be masked to the active vs sham stimulation settings, it is single blinded i.e. study participants are not aware if active or sham stimulation is occurring but the investigator is aware
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Physician in Geriatric and Stroke Medicine, Director Institute of Memory and Cognition, Associate Professor of Medical Gerontology, Trinity College Dublin

Study Record Dates

• First Submitted: July 29, 2022
• First Posted: August 24, 2022
• Study Start: June 1, 2022
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)