Clinical trial NCT04877782: Modulating the Locus Coeruleus Function
Official title: Boosting a Neuromodulatory System Relevant to Alzheimer's Disease to Enhance Memory
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy Aging
Keywords: Healthy aging
Transcutaneous vagus nerve stimulation
Magnetic resonance imaging
Locus coeruleus
Memory and attention
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: University of Liege
First posted: 2021-05-07
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy older individuals participating in the study will be recruited from the community.

Brief summary: The purpose of this study is to investigate the impact of transcutaneous vagus nerve stimulation (tVNS) on specific brain regions involved in memory and attention processes.

tVNS is a non-invasive and non-pharmacological technique known for targeting the locus coeruleus, a small subcortical nucleus in the brain thought to be involved in the earliest stages of Alzheimer's disease. This nucleus also plays a role in numerous cognitive functions, comprising memory and attention.

Detailed description: This study is an observational MRI study with a pseudo-randomized single blind cross-over design. The population consists of 30 healthy human volunteers from 60 to 80 years old. These healthy older individuals will be recruited from the community.

After being informed about the study protocol and the potential risks, subjects will be given 1 week to consider their participation.

All participants giving written informed consent will be included in the study. The first session will consist in neuropsychological assessments and a task practice session in the dummy scanner in order to get familiar with the environment. Participants meeting the eligibility criteria will be included for the next sessions.

The second and third sessions are MRI scanning sessions including transcutaneous vagus nerve stimulation. Both the placebo and experimental stimulation conditions will be randomized in a single-blind manner across scanning sessions.

About 7 to 10 weeks after each scanning session and at least 4 days previous to the next MRI session, participant will be asked to fill in an online memory test for assessing potential outlasting effects of the stimulation technique.

Eligibility criteria: Inclusion Criteria:

* Average neuropsychological test results in accordance with normative data corrected for age, education and sex
* No substantial memory complaints according to the participant
* Body mass index \< 28
* Non-smoking
* Right handedness
* Average/high level of education (minimum 12 years of education)

Exclusion Criteria:

* Psychoactive medication use
* Abuse of alcohol and drugs
* Cognitive impairment due to alcohol/drug or other substances abuse
* Recent trans-meridian travel (\<2months)
* Night shift work (\<1year)
* Diabetes if not stable
* Hypo-/hyper-tension, hypo-/hyper-thyroid if not stable
* Hypo-tension due to autonomic dysfunction
* Recent (\<5years) or present psychiatric or neurological disorders (anxiety, major depression, schizophrenia, bipolar disorder, psychotic disorder -or treatment for it-, epilepsy, stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, brain surgery, brain trauma, electroshock therapy, kidney dialysis, Ménière's disease, brain infections)
* Major vascular disorders (e.g. stroke)
* History of cardiovascular disorders (e.g., severe heart failure, recurrent vasovagal syncopal episodes)
* Major valvular disorders (e.g., prosthetic valve or hemodynamically relevant valvular disease, unilateral or bilateral vagotomy)
* Contraindications for scanning (e.g., brain surgery, cardiac pacemaker, metal implants, claustrophobia, body tattoos, reduced vision even after appropriate optical correction)
* Contraindications for pupil measurements and light exposure (e.g., Cataracts, Glaucoma, detached retina's, eye surgery involving the muscle, penetrating eye wounds, use of cholinesterase inhibitors, anticholinergic eye drop use, droopy eyelids preventing eye measurement).

Primary outcomes:
measure: Pupillometry - Scan session 1
timeFrame: During the first MRI scanning session (55 minutes)
measure: Pupillometry - Scan session 2
timeFrame: During the second MRI scanning session (55 minutes)
measure: Blood oxygen level dependent (BOLD) response - Scan session 1
timeFrame: During the first MRI scanning session (55 minutes)
measure: Blood oxygen level dependent (BOLD) response - Scan session 2
timeFrame: During the second MRI scanning session (55 minutes)
Secondary outcomes:
measure: Performance on the online memory task - Post-session 1
timeFrame: Performed from home, 7 to 10 days after the first MRI session and at least 4 days prior to the second session.
measure: Performance on the online memory task - Post-session 2
timeFrame: Performed from home, 7 to 10 days after the second MRI session.
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
Study officials:
affiliation: Maastricht University
name: Heidi IL Jacobs, Dr.
role: PRINCIPAL_INVESTIGATOR
References: