Clinical trial NCT04908358: The Wandering Nerve: Gateway to Boost Alzheimer's Disease Related Cognitive Performance
Official title: The Wandering Nerve: Gateway to Boost Alzheimer's Disease Related Cognitive
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aging
Keywords: Transcutaneous vagus nerve stimulation
Memory
Brainstem
Aging
Preclinical Alzheimer's disease
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2021-06-01
Enrollment: 140
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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

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.

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
* 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

Primary outcomes:
measure: Performance on the Face-name association memory task (FNAME)
timeFrame: Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25
measure: Being a responder as determined by Face-name association memory task (FNAME) change scores
timeFrame: Based on data from the first 4 weeks (cross-over)
Secondary outcomes:
measure: 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.
timeFrame: Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25
measure: Change in inflammatory responses (aggregated)
timeFrame: Assessed during the first week and during week 9
measure: Change in inflammatory responses (interleukins)
timeFrame: Assessed during the first week and during week 9
measure: Change in inflammatory responses (TNF)
timeFrame: Assessed during the first week and during week 9
measure: Change in inflammatory responses (MIP)
timeFrame: Assessed during the first week and during week 9
measure: Change in inflammatory responses (MCP)
timeFrame: Assessed during the first week and during week 9
measure: Change in inflammatory responses (C)
timeFrame: Assessed during the first week and during week 9
measure: Change in inflammatory responses (TREM)
timeFrame: Assessed during the first week and during week 9
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Heidi IL Jacobs, PhD
role: PRINCIPAL_INVESTIGATOR
References: