The Wandering Nerve: Gateway to Boost Alzheimer's Disease Related Cognitive Performance

NCT ID: NCT04908358

Last Updated: 2026-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-24

Study Completion Date

2026-04-30

Brief Summary

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In this research study the investigators want to find out if a non-invasive electrical brain stimulation method called RAVANS (also called tVNS) can have a beneficial effect on cognition in older individuals. The investigators also want to understand whether certain individual factors contribute to the effect of RAVANS on cognition. RAVANS is only used in research studies.

Detailed Description

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The intervention will be studied in 140 older individuals using a randomized cross-over design of sham versus RAVANS stimulation (2 sessions separated by 4 weeks) during a functional magnetic resonance imaging (fMRI) task. Participants will then be randomized to daily tVNS or sham sessions during 10 visits within two weeks, and two follow-up cognitive assessments each after 2 months of the last intervention session. The face-name association task will be the main outcome measure. The investigators will also draw blood twice to examine whether the response on the outcome is dependent on Alzheimer's disease related biomarker, and whether RAVANS has effects on inflammatory responses.

Conditions

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Aging

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Randomized cross-over followed by placebo-controlled study (allocation to placebo or control condition takes APOE-E4 status into account and the previous ordering of the cross-over design)
Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Participants
Participant will not be informed of condition. The investigators will work with blinded data (but can know the condition during intervention)

Study Groups

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Sham preceded by cross-over Sham-Stimulation

Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Wash-out period of four weeks Ten daily sessions of sham during 2 weeks

Group Type SHAM_COMPARATOR

Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Sham stimulation of vagus nerve in the outer ear

Sham preceded by cross-over Stimulation-Sham

Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by Sham Wash-out period of four weeks Ten daily sessions of sham during 2 weeks

Group Type SHAM_COMPARATOR

Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Sham stimulation of vagus nerve in the outer ear

Stimulation preceded by cross-over Sham-Stimulation

Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Wash-out period of four weeks Ten daily sessions of RAVANS during 2 weeks

Group Type EXPERIMENTAL

Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Stimulation of vagus nerve in the outer ear

Stimulation preceded by cross-over Stimulation-Sham

Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by sham Wash-out period of four weeks Ten daily sessions of RAVANS during 2 weeks

Group Type EXPERIMENTAL

Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Stimulation of vagus nerve in the outer ear

cross-over Stimulation-Sham

Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by sham One time RAVANS versus one time Sham Two weeks wash-out

Group Type OTHER

Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Stimulation of vagus nerve in the outer ear

Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Sham stimulation of vagus nerve in the outer ear

cross-over Sham-Stimulation

Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) One time RAVANS versus one time Sham Two weeks wash-out

Group Type OTHER

Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Stimulation of vagus nerve in the outer ear

Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Intervention Type OTHER

Sham stimulation of vagus nerve in the outer ear

Interventions

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Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Stimulation of vagus nerve in the outer ear

Intervention Type OTHER

Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions

Sham stimulation of vagus nerve in the outer ear

Intervention Type OTHER

Other Intervention Names

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Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) transcutaneous vagus nerve stimulation Sham Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Sham transcutaneous vagus nerve stimulation

Eligibility Criteria

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Inclusion Criteria

* Fluent in English
* Willingness and ability to comply with scheduled visits, magnetic resonance imaging (MRI) scanning, laboratory tests, and other study procedures.
* Subjects with well-controlled vascular risk factors, such as treated hypertension, treated hyperlipidemia or well controlled Type II diabetes will be included.
* Stable medications for at least 30 days.
* Mini Mental State Exam adjusted for age and education of 25 to 30, inclusive or a Telephone Interview for Cognitive Status score of at least 32
* Perform within 1.5 S.D. of age and education matched norms on the Logical Memory Paragraph Delayed Recall
* Geriatric Depression Scale \< 11
* Aged 60-85, inclusive
* Right-handed
* Reduced vision is allowed if it can be corrected with MRI-goggles

Exclusion Criteria

* Prior known diagnosis of mild cognitive impairment (MCI) or dementia
* Use of investigational drugs or devices within 60 days prior to screening
* Subjects with contraindications to MRI cannot participate (i.e., implanted metal including pacemakers, cerebral spinal fluid shunts, aneurysm clips, artificial heart valves, ear implants or metal/foreign objects in the eyes and those with a history of claustrophobia)
* Pregnant.
* Major psychiatric disorders such as schizophrenia, schizoaffective disorder, major affective disorder in mid-life, or treatment with electroconvulsive therapy (ECT) (Mild depression that is well treated with stable dose of selective serotonergic reuptake inhibitor (SSRI) antidepressants will be allowed).
* Have a history of major head trauma defined as a loss of consciousness and/or trauma requiring hospitalization
* Substance abuse within the past 2 years
* Active hematological, renal, pulmonary, endocrine or hepatic disorders.
* Evidence of cortical infarcts or strategically placed lacunar infarct (e.g. dorsal medial nucleus of thalamus). MRI evidence of mild white matter signal abnormalities will be allowed.
* Active cancer, metabolic encephalopathy, infection
* Active cardiovascular disease, stroke, congestive or severe heart failure
* Huntington's disease, hydrocephalus or seizure disorder
* Cataracts, glaucoma, detached retina's, eye surgery involving the muscles; droopy eyelids, penetrating eye wounds and use of anticholinergic eye drop use
* Weight equal to or greater than 300 lbs (weight limit of the MRI table).
* Recurrent vaso-vagal syncopal episodes
* Unilateral or bilateral vagotomy
* Severe valvular disorder (i.e. prosthetic valve or hemodynamically relevant valvular diseases)
* Sick sinus syndrome
* Hypotension due to autonomic dysfunction
Minimum Eligible Age

60 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Heidi Jacobs

Associate Professor of Radiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Heidi IL Jacobs, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Charlestown, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Heidi IL Jacobs, PhD

Role: CONTACT

6179097679

Nina Engels, PhD

Role: CONTACT

617-724-5354

Facility Contacts

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Heidi IL Jacobs, PhD

Role: primary

Other Identifiers

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1R01AG068062-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2021P000498

Identifier Type: -

Identifier Source: org_study_id

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