The Wandering Nerve: Gateway to Boost Alzheimer's Disease Related Cognitive
Overview
- Phase
- Not Applicable
- Intervention
- Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions
- Conditions
- Aging
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 126
- Locations
- 1
- Primary Endpoint
- Being a responder as determined by Face-name association memory task (FNAME) change scores
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
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.
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.
Investigators
Heidi Jacobs
Associate Professor of Radiology
Massachusetts General Hospital
Eligibility Criteria
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
Arms & Interventions
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
Intervention: 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
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
Intervention: 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
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
Intervention: 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
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
Intervention: Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions
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
Intervention: Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions
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
Intervention: Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions
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
Intervention: Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions
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
Intervention: Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions
Outcomes
Primary Outcomes
Being a responder as determined by Face-name association memory task (FNAME) change scores
Time Frame: Based on data from the first 4 weeks (cross-over)
Participants are grouped in being a responder (1) or non-responder (0).
Performance on the Face-name association memory task (FNAME)
Time Frame: Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25
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).
Secondary Outcomes
- 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 (MCP)(Assessed during the first week and during week 9)
- 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)
- Change in inflammatory responses (C)(Assessed during the first week and during week 9)
- Change in inflammatory responses (TREM)(Assessed during the first week and during week 9)