AgingNCT04276805
Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults
A study testing Transcutaneous vagal nerve stimulation (tVNS) and Cognitive training in people with Aging, run by University of Florida at 2 sites in United States.
Trial summary
Decline in brain health and associated loss of cognitive function in healthy aging decreases quality of life.We need better tools to both enhance brain health and improve cognitive performance in healthy brain aging so that it can be delayed, reduced, or even reversed. Read more about this study
- Who is it for?
- Ages 65 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Transcutaneous vagal nerve stimulation (tVNS) and Cognitive training
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Nov 2020to 27 Sep 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 90 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Healthy individuals willing to commit to study requirements
Who cannot join
- Neurological disorders to include traumatic brain injury.
- Evidence of dementia .
- Major psychiatric illness
- Unstable and chronic medical conditions.
- MRI contraindications (e.g., pregnancy, claustrophobia, metal implants that are contraindicated for MRI).
- Physical impairment precluding motor response or lying still or walking
- Hearing or vision deficits that will not allow for completion of assessments
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32610
University of Arizona
Tucson, Arizona, 85721
About this study
Decline in brain health and associated loss of cognitive function in healthy aging decreases quality of life.We need better tools to both enhance brain health and improve cognitive performance in healthy brain aging so that it can be delayed, reduced, or even reversed. The present proposal is designed to evaluate the pairing of cognitive training with a non-invasive neurostimulation technology that has shown promise in both increasing neuroplasticity and in enhancing cognitive performance, transcutaneous vagal nerve stimulation (tVNS).
Read the detailed description
Decline in brain health and associated loss of cognitive function in healthy aging decreases quality of life. We need better tools to both enhance brain health and improve cognitive performance in healthy brain aging so that it can be delayed, reduced, or even reversed. Auricular or transcutaneous vagal nerve stimulation (tVNS) is a low cost, easy to use, safe, and non-invasive approach for potentially enhancing brain systems important for cognition, neuroplasticity, and brain health.
The afferent path of the vagus travels through the nucleus of the solitary tract and the locus coeruleus, which both project to the hippocampus, a structure important in encoding new memories. The locus coeruleus is also the brain's primary source of norepinephrine. As the brain ages, there is a significant decline in the number and health of neurons, including in the pathway of the locus coeruleus. The release of norepinephrine in the medial temporal regions including the hippocampus, and the frontal lobes may enhance synaptic plasticity in critical cognitive areas and VNS upregulates norepinephrine.
The present proposal is designed to evaluate the pairing of cognitive training with transcutaneous vagal nerve stimulation (tVNS). The investigators have a collaborative relationship with the phase III Augmenting Cognitive Training (ACT) study team, which pairs a different non-invasive approach to brain stimulation (tDCS) with cognitive training. The investigators will leverage the existing ACT infrastructure developed through the support of NIA and the MBRF to evaluate tVNS and a cognitive training program in a two-week intervention with before and after cognition and multi-modal MRI assessments to determine brain function, plasticity, and cognitive modifications resulting from the intervention.
- Conditions
- Aging
- Being tested
- Transcutaneous vagal nerve stimulation (tVNS), Cognitive training
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous vagal nerve stimulation (tVNS)Device
The active tVNS group will receive non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. The sham group will receive sham stimulation (0x sensory threshold) using electrodes placed on the left earlobe.
Cognitive trainingBehavioural
Cognitive training will be delivered for one hour daily over a two-week period via a web-based program (Posit Science BrainHQ, accessed through www.positscience.com) containing eight adaptive tasks targeting attention, processing speed, and working memory. Participants will complete four randomly selected tasks per hour of training.
| Study group | Role | What they receive |
|---|---|---|
| tVNS group | Active comparator | Participants will be randomly assigned to receive either active tVNS or sham stimulation during two weeks of cognitive training and will complete assessments before and after completion of this intervention. Participants in the tVNS group will undergo cognitive training paired with tVNS. Receives: Device: Transcutaneous vagal nerve stimulation (tVNS); Behavioral: Cognitive training |
| Sham group | Sham comparator | Participants will be randomly assigned to receive either active tVNS or sham stimulation during two weeks of cognitive training and will complete assessments before and after completion of this intervention. Participants in the tVNS group will undergo cognitive training paired with sham stimulation. Receives: Behavioral: Cognitive training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hopkins Verbal Learning Test (Total Immediate Recall)
The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. The total immediate recall score is the sum of correct words recalled after each of the 3 learning trials, which can range from 0 to 36.
Measured: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
Hopkins Verbal Learning Test (Total Delayed Recall)
The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. The total delayed recall score is the number of total correct words recalled (ranging from 0 to 12) after a 20-25 minute delay.
Measured: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
Hopkins Verbal Learning Test (Total Retention)
The Hopkins Verbal Learning Test-Revised (HVLT-R) is a verbal learning and memory measure involving learning a 12-item word list across three learning trials followed by delayed recall after approximately 20-25 minutes. The Total Retention score is calculated by dividing the delayed recall score (range: 0-12) by the higher score from Learning Trial 2 or Learning Trial 3 (range: 0-12) and multiplying by 100 to yield the percentage of words retained following the delay period. Higher percentage scores indicate better retention of learned information. A score of 100% indicates that delayed recall performance was equal to the participant's best learning trial. Percentage scores greater than 100% are possible when delayed recall performance exceeds the participant's highest score on Learning Trial 2 or Learning Trial 3.
Measured: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
Hopkins Verbal Learning Test (Recognition)
The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. Within the delayed yes-no recognition part of the task, the participant is presented with a larger list or words and responds to whether each was on the original 12-item list. The recognition discrimination index score is calculated as number of hits (correctly identified words from the list) - number of false positive words (incorrectly identified words that were not on the list), with scores ranging from 0 to 12 (perfect score).
Measured: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
NIH Toolbox Fluid Cognitive Composite
The National Institutes of Health (NIH) Toolbox Fluid Cognition Composite is a standardized measure of fluid cognitive functioning derived from performance on five tests assessing attention, executive function, working memory, episodic memory, and processing speed (Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, Picture Sequence Memory, List Sorting Working Memory, and Pattern Comparison). Scores are reported as Fully Corrected T-scores derived from NIH Toolbox normative data and adjusted for demographic characteristics including age, sex, race/ethnicity, and education. Fully Corrected T-scores have a normative mean of 50 and standard deviation of 10. Higher T-scores indicate better fluid cognitive functioning, whereas lower T-scores indicate poorer fluid cognitive functioning. A T-score of 50 represents average performance relative to the normative population.
Measured: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start17 Nov 2020
- Primary completion27 Sep 2024
- Study completion27 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- University of Arizona
- Responsible party
- Sponsor
- Investigators
- John Williamson, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276805
- Sponsor's protocol ID
- IRB201902991
- Status last verified
- Apr 2025
- First submitted
- 17 Feb 2020
- Last updated
- 27 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults
- ClinicalTrials.gov ID
- NCT04276805
- Acronym / sponsor ID
- IRB201902991
- Conditions
- Aging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- University of Arizona
- Study start
- 17 Nov 2020 (actual)
- Primary completion
- 27 Sep 2024 (actual)
- Study completion
- 27 Sep 2024 (actual)
- First posted
- 19 Feb 2020 (actual)
- Results
- Posted 27 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Decline in brain health and associated loss of cognitive function in healthy aging decreases quality of life.We need better tools to both enhance brain health and improve cognitive performance in healthy brain aging so that it can be delayed, reduced, or even reversed. The present proposal is designed to evaluate the pairing of cognitive training with a non-invasive neurostimulation technology that has shown promise in both increasing neuroplasticity and in enhancing cognitive performance, transcutaneous vagal nerve stimulation (tVNS).
Detailed description
Decline in brain health and associated loss of cognitive function in healthy aging decreases quality of life. We need better tools to both enhance brain health and improve cognitive performance in healthy brain aging so that it can be delayed, reduced, or even reversed. Auricular or transcutaneous vagal nerve stimulation (tVNS) is a low cost, easy to use, safe, and non-invasive approach for potentially enhancing brain systems important for cognition, neuroplasticity, and brain health.
The afferent path of the vagus travels through the nucleus of the solitary tract and the locus coeruleus, which both project to the hippocampus, a structure important in encoding new memories. The locus coeruleus is also the brain's primary source of norepinephrine. As the brain ages, there is a significant decline in the number and health of neurons, including in the pathway of the locus coeruleus. The release of norepinephrine in the medial temporal regions including the hippocampus, and the frontal lobes may enhance synaptic plasticity in critical cognitive areas and VNS upregulates norepinephrine.
The present proposal is designed to evaluate the pairing of cognitive training with transcutaneous vagal nerve stimulation (tVNS). The investigators have a collaborative relationship with the phase III Augmenting Cognitive Training (ACT) study team, which pairs a different non-invasive approach to brain stimulation (tDCS) with cognitive training. The investigators will leverage the existing ACT infrastructure developed through the support of NIA and the MBRF to evaluate tVNS and a cognitive training program in a two-week intervention with before and after cognition and multi-modal MRI assessments to determine brain function, plasticity, and cognitive modifications resulting from the intervention.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tVNS group | Active comparator | Device: Transcutaneous vagal nerve stimulation (tVNS), Behavioral: Cognitive trainingParticipants will be randomly assigned to receive either active tVNS or sham stimulation during two weeks of cognitive training and will complete assessments before and after completion of this intervention. Participants in the tVNS group will undergo cognitive training paired with tVNS. |
| Sham group | Sham comparator | Behavioral: Cognitive trainingParticipants will be randomly assigned to receive either active tVNS or sham stimulation during two weeks of cognitive training and will complete assessments before and after completion of this intervention. Participants in the tVNS group will undergo cognitive training paired with sham stimulation. |
Who may qualify
- Ages
- 65 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- Healthy individuals willing to commit to study requirements
Key exclusion criteria (7 listed)
- Neurological disorders to include traumatic brain injury.
- Evidence of dementia .
- Major psychiatric illness
- Unstable and chronic medical conditions.
- MRI contraindications (e.g., pregnancy, claustrophobia, metal implants that are contraindicated for MRI).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous vagal nerve stimulation (tVNS)The active tVNS group will receive non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. The sham group will receive sham stimulation (0x sensory threshold) using electrodes placed on the left earlobe. | Device | tVNS group |
| Cognitive trainingCognitive training will be delivered for one hour daily over a two-week period via a web-based program (Posit Science BrainHQ, accessed through www.positscience.com) containing eight adaptive tasks targeting attention, processing speed, and working memory. Participants will complete four randomly selected tasks per hour of training. | Behavioural | Sham group, tVNS group |
Primary outcome
Hopkins Verbal Learning Test (Total Immediate Recall)
Time frame: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. The total immediate recall score is the sum of correct words recalled after each of the 3 learning trials, which can range from 0 to 36.
Hopkins Verbal Learning Test (Total Delayed Recall)
Time frame: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. The total delayed recall score is the number of total correct words recalled (ranging from 0 to 12) after a 20-25 minute delay.
Hopkins Verbal Learning Test (Total Retention)
Time frame: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
The Hopkins Verbal Learning Test-Revised (HVLT-R) is a verbal learning and memory measure involving learning a 12-item word list across three learning trials followed by delayed recall after approximately 20-25 minutes. The Total Retention score is calculated by dividing the delayed recall score (range: 0-12) by the higher score from Learning Trial 2 or Learning Trial 3 (range: 0-12) and multiplying by 100 to yield the percentage of words retained following the delay period. Higher percentage scores indicate better retention of learned information. A score of 100% indicates that delayed recall performance was equal to the participant's best learning trial. Percentage scores greater than 100% are possible when delayed recall performance exceeds the participant's highest score on Learning Trial 2 or Learning Trial 3.
Hopkins Verbal Learning Test (Recognition)
Time frame: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. Within the delayed yes-no recognition part of the task, the participant is presented with a larger list or words and responds to whether each was on the original 12-item list. The recognition discrimination index score is calculated as number of hits (correctly identified words from the list) - number of false positive words (incorrectly identified words that were not on the list), with scores ranging from 0 to 12 (perfect score).
NIH Toolbox Fluid Cognitive Composite
Time frame: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).
The National Institutes of Health (NIH) Toolbox Fluid Cognition Composite is a standardized measure of fluid cognitive functioning derived from performance on five tests assessing attention, executive function, working memory, episodic memory, and processing speed (Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, Picture Sequence Memory, List Sorting Working Memory, and Pattern Comparison). Scores are reported as Fully Corrected T-scores derived from NIH Toolbox normative data and adjusted for demographic characteristics including age, sex, race/ethnicity, and education. Fully Corrected T-scores have a normative mean of 50 and standard deviation of 10. Higher T-scores indicate better fluid cognitive functioning, whereas lower T-scores indicate poorer fluid cognitive functioning. A T-score of 50 represents average performance relative to the normative population.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Williamson, PhD principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous vagal nerve stimulation (tVNS) and Cognitive training in people with Aging, run by University of Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hopkins Verbal Learning Test (Total Immediate Recall) (time frame: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.