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

NCT04908358 | Active Not Recruiting DMC

• 2 other identifiers: 2021P0004981R01AG068062-01A1
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aging

Keywords

Transcutaneous vagus nerve stimulation; Memory; Brainstem; Aging; Preclinical Alzheimer's disease

Outcome Measures

Primary Outcomes (2)

• Performance on the Face-name association memory task (FNAME)

  Change from baseline at each visit where FNAME is completed: Scores are z-scores with a mean of zero. Higher scores are better (there is no minimum/maximum).

  Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25

• Being a responder as determined by Face-name association memory task (FNAME) change scores

  Participants are grouped in being a responder (1) or non-responder (0).

  Based on data from the first 4 weeks (cross-over)

Secondary Outcomes (8)

• Performance on other cognitive composite scores: this includes a composite score of memory, a composite score of executive function and the Preclinical Alzheimer's disease cognitive composite.

  Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25

• Change in inflammatory responses (aggregated)

  Assessed during the first week and during week 9

• Change in inflammatory responses (interleukins)

  Assessed during the first week and during week 9

• Change in inflammatory responses (TNF)

  Assessed during the first week and during week 9

• Change in inflammatory responses (MIP)

  Assessed during the first week and during week 9

Study Arms (6)

Sham preceded by cross-over Sham-Stimulation

SHAM COMPARATOR

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

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

Sham preceded by cross-over Stimulation-Sham

SHAM COMPARATOR

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

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

Stimulation preceded by cross-over Sham-Stimulation

EXPERIMENTAL

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

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

Stimulation preceded by cross-over Stimulation-Sham

EXPERIMENTAL

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

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

cross-over Stimulation-Sham

OTHER

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

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

cross-over Sham-Stimulation

OTHER

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

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

Interventions

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

Stimulation of vagus nerve in the outer ear

Also known as: Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), transcutaneous vagus nerve stimulation

Stimulation preceded by cross-over Sham-Stimulation; Stimulation preceded by cross-over Stimulation-Sham; cross-over Sham-Stimulation; cross-over Stimulation-Sham

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

Sham stimulation of vagus nerve in the outer ear

Also known as: Sham Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), Sham transcutaneous vagus nerve stimulation

Sham preceded by cross-over Sham-Stimulation; Sham preceded by cross-over Stimulation-Sham; cross-over Sham-Stimulation; cross-over Stimulation-Sham

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Study Officials

• Heidi IL Jacobs, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant will not be informed of condition. The investigators will work with blinded data (but can know the condition during intervention)
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiology

Model Details: 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)

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: June 1, 2021
• Study Start: November 24, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Consistent with NIH regulations, as provided in the manual of the NIH (SF424 (R\&R)), data will be made available at the time of publication of the primary results or within 9 months of database lock, whichever comes first, and will be available for at least 3 years or until the sharing platform is no longer available. A more detailed plan for sharing data and a data user agreement procedure will be set up during the study.
• Access Criteria: Access to the clinical trial IPD can be requested by qualified scientists affiliated a research institutions, and will be provided following review and approval of a research proposal, statistical analysis plan and after signing a data user agreement. Requests can be submitted to wallestudy@mgh.harvard.edu from the first publication date of the primary results or within 9 months of database lock, whichever comes first. In the future, more information on data requests can be found on http://www.heidijacobs.org/. A more detailed plan for sharing data and a data user agreement procedure will be set up during the study.

Locations

US (1)