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

Mass General Brigham

Status: Enrolling

Conditions: Aging

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04908358

2021P000498

1R01AG068062-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 140 estimated patients

Sex: All

Ages: 60 to 85 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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140 participants in 6 patient groups

Sham preceded by cross-over Sham-Stimulation

Sham Comparator group

Description:

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

Treatment:

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 group

Description:

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

Treatment:

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 group

Description:

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

Treatment:

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 group

Description:

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

Treatment:

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

cross-over Stimulation-Sham

Other group

Description:

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

Treatment:

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 group

Description:

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

Treatment:

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