Vagus Nerve Stimulation to Enhance Memory in Aging

NCT07214194 | Not Yet Recruiting FDA Device

• 1 other identifier: VNS102025
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to determine whether non-invasive vagus nerve stimulation enhances memory formation in cognitively healthy older adults and whether the effects of stimulation depend on gut and brain health.

Conditions

Alzheimer Disease; Aging

Outcome Measures

Primary Outcomes (1)

• Change in Recognition Memory (d-prime)

  d' is a signal-detection sensitivity index-how well participants discriminate old (studied) from new (unstudied) items, independent of response bias. Computed as d' = Z(hit rate) - Z(false-alarm rate) from the old/new recognition memory test. Primary analysis is within-person Δhigh-confidence d' (based on "sure old" responses in the 4-point "sure old", "unsure old", "unsure new", "sure new" scale, Δ = active - sham) and Δoverall d' (based on "sure old" and "unsure old" responses). Main comparison is older vs. young, and within the older group also testing moderation by gut-brain axis measures and interactions with preclinical Alzheimer's disease pathology (pTau217, pTau181, Aβ42:40).

  post-active vs post-sham stimulation; up to 2 hours of task

Study Arms (2)

Active vagus nerve stimulation

EXPERIMENTAL

Participants will receive active stimulation during memory encoding of picture-word pairs. Active stimulation will occur during two learning phases of the learning and memory task. The total duration of these two phases will be less than 30 minutes.

Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Sham stimulation

SHAM COMPARATOR

Participants will receive sham stimulation during memory encoding of picture-word pairs. Sham stimulation will occur during two learning phases of the learning and memory task. The total duration of these two phases will be less than 30 minutes.

Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Interventions

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) DEVICE

Non-invasive vagus nerve stimulation will be delivered with a well-validated device. taVNS delivers stimulation on the left ear, with the placement of the stimulating electrode differing between the active and sham conditions. Stimulation will occur during each learning trial (total of 30 trials per phase).

Active vagus nerve stimulation; Sham stimulation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-30 years or 65-80 years
• Normal or corrected-to-normal vision (visual acuity)
• Fluent in English

You may not qualify if:

• Pregnant
• Symptoms of memory loss
• History of a neurological, psychiatric, or medical condition that could affect cognition or preclude MRI or pupillometry
• Use of medications known to alter cognition
• For older adults, neuropsychological performance that falls outside 1.5 standard deviations of age-adjusted norms and no self-reported memory or attention complaints

Sponsors & Collaborators

• Stanford University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Anthony D Wagner, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Because the active electrode will be placed on the cymba conchae and the sham on the earlobe, full double-blinding is not feasible; as such, the experimenter will be aware of the active/sham condition status of each experimental block. Participants will be masked/blinded to condition order and hypotheses (they will not be informed which blocks are active vs. sham).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Psychology

Model Details: The study will use a sham-controlled, single-blind, within-subject, counterbalanced, randomized design. Each participant will complete four blocks (two active and two sham stimulation) in a counterbalanced within-subject design using an ABBA or BAAB order (A = active taVNS, B = sham stimulation). To ensure equal numbers per order, order will be deterministically assigned by subject ID parity: odd = ABBA, even = BAAB. Subject IDs will be issued sequentially within the age group, yielding balance in both Young and Older groups and effective random assignment of participants to order condition.

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: October 9, 2025
• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: The data will be made available upon publication of corresponding results or at the end of the award period, whichever is sooner. They will remain available indefinitely or until the end-of-life of the corresponding data-hosting platforms, if no suitable alternative can be identified.
• Access Criteria: De-identified MRI and other components of the dataset will be findable and identifiable via persistent Stanford Digital Repository (SDR) URLs. These links will be embedded in published preprints and manuscripts, as well as with direct links on the Stanford Memory Lab's webpage. The SDR does not require data to be associated with a publication to be accepted by the repository. Processed microbiome data tables and metadata will be findable and identifiable through GEO accession numbers. The raw sequencing data will be findable and identifiable through SRA accession numbers. Access to de-identified data will not be controlled (i.e., once publicly available, anyone can access the de-identified data).

Locations

US (1)