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Purpose

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.

Condition

Eligibility

Eligible Ages
Between 60 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
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 Purpose
Other
Masking
Single (Participant)
Masking Description
Participant will not be informed of condition. The investigators will work with blinded data (but can know the condition during intervention)

Arm Groups

ArmDescriptionAssigned Intervention
Sham Comparator
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
  • 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
    Other names:
    • Sham Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • Sham transcutaneous vagus nerve stimulation
Sham Comparator
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
  • 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
    Other names:
    • Sham Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • Sham transcutaneous vagus nerve stimulation
Experimental
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
  • Other: 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
    Other names:
    • Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • transcutaneous vagus nerve stimulation
Experimental
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
  • Other: 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
    Other names:
    • Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • transcutaneous vagus nerve stimulation
Other
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
  • Other: 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
    Other names:
    • Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • transcutaneous vagus nerve stimulation
  • 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
    Other names:
    • Sham Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • Sham transcutaneous vagus nerve stimulation
Other
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
  • Other: 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
    Other names:
    • Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • transcutaneous vagus nerve stimulation
  • 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
    Other names:
    • Sham Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS)
    • Sham transcutaneous vagus nerve stimulation

Recruiting Locations

Massachusetts General Hospital
Charlestown, Massachusetts 02129
Contact:
Heidi IL Jacobs, PhD

More Details

Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

Heidi IL Jacobs, PhD
6179097679
hjacobs@mgh.harvard.edu

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.