Healthy Young AdultsNCT03628976
Noninvasive Vagus Nerve Stimulation (VNS) for Neuromotor Adaptations
A study testing tVNS and Motor training in people with Healthy Young Adults, run by Georgia Institute of Technology at 1 site in United States.
Trial summary
The study will examine how electrical stimulation of vagus nerve (i.e. nerve around the outer ear) from the skin surface during motor training influences a brain hormone (called norepinephrine), brain activity, and motor performance. Read more about this study
- Who is it for?
- Ages 18 to 39 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Young Adults
- What is being tested?
- tVNS and Motor training
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 20 May 2019to 28 Jun 2021
- 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 18 to 39 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women in the age range of 18-39 years will be recruited. All subjects will be healthy and right-handed. Subjects will match the ethnic distribution in the local community.
Who cannot join
- To ensure the safety associated with TMS and transcutaneous afferent vagus nerve stimulation, following adults will be excluded as in our previous studies (Buharin et al. 2013, 2014) and following the standard recommendations (Keel et al. 2001):
- Younger than 18 years old or older than 39 years old
- Left-handed
- Skilled use of hands (e.g. professional musician)
- High blood pressure (>140/90 mmHg)
- Had cardiovascular problems
Show all 25Show fewer
- Obese (Body Mass Index: > 30 kg/m2)
- Had sensory deficits in your limb
- Had alcoholism
- Had psychiatric disorders
- Had an adverse reaction to TMS (a technique for non-invasive neural stimulation from the brain)
- Had a seizure (an abnormal phenomenon of the brain marked by temporary abnormal neuronal activity. Symptoms include involuntary changes in body movement or function, sensation, awareness, or behavior.)
- Someone in your family has epilepsy (recurrent seizures marking excessive synchronous neuronal activity in the brain)
- Had an EEG (measurement of the electrical activity of the brain through the use of surface electrodes placed on the scalp) for clinical diagnosis
- Had a stroke (the loss of brain function due to an interruption in the blood supply to the brain)
- Had a head injury (include neurosurgery) that required a visit to a hospital
- Suffer from frequent or severe headaches (e.g., migraine headaches within the last six months)
- Have any metal permanently in your head (outside the mouth) such as shrapnel, surgical clips, or fragments from welding or metal work. Piercings and other metals on your head are OK if they will be removed before the study.
- Have any implanted devices such as cardiac pacemakers (a medical device that uses electrical signals to regulate heart beat), medical pumps, or intra-cardiac lines
- Had any other brain-related condition
- Had any illness that caused brain injury (i.e. meningitis, aneurysm, brain tumor)
- Had severe disease such as cardiologic, pulmonary, renal, endocrinal (hyperthyroidism or hypothyroidism), gastrointestinal or others.
- Taking any medications other than over-the-counter medicine
- Suspect you might be pregnant (if woman)
- Have hearing problems, such as impaired hearing, tinnitus, etc.
Trial locations and contacts
1 site in 1 country.
United States1 site
Human Neuromuscular Physiology Lab
Atlanta, Georgia, 30332
About this study
The study will examine how electrical stimulation of vagus nerve (i.e. nerve around the outer ear) from the skin surface during motor training influences a brain hormone (called norepinephrine), brain activity, and motor performance.
Read the detailed description
Motor function is compromised with advanced age, and motor impairment is involved in various neuromotor injuries and disorders including stroke, spinal cord injury, amputation, and aging. Development of effective interventions for facilitating neuromotor adaptation is essential for accelerating or augmenting rehabilitation outcomes in the control of impaired limbs. The ultimate goal of the study is to find non-pharmacological and non-invasive neuromodulating interventions for enhancing the rehabilitation outcomes that may be applied to individuals with impaired motor function. In rats, implanted afferent vagus nerve stimulation paired with motor training enhanced neuromotor adaptation and motor recovery most likely through increased release of central neuromodulators that originate from the brainstem. The investigators propose to translate the findings in rats into humans by applying vagus nerve stimulation noninvasively. Transcutaneous VNS (tVNS) can noninvasively activate the brainstem including locus coeruleus, where norepinephrine (i.e. neuromodulator) is synthesized. However, it is unknown whether tVNS leads to increasing neuromodulators and facilitating neuromotor adaptations when combined with motor training in humans. With potential applicability of this novel intervention for facilitating neuromotor adaptation to various clinical human populations in future scope, it is essential to start with the basic understanding about the effect of tVNS on the neuromotor system and training-induced adaptation in neuromotor behavior in non-disabled humans. The overarching hypothesis is that an application of tVNS increases central norepinephrine and facilitates training-induced neuromotor adaptations in humans. The specific aim is to examine the effect of tVNS on central norepinephrine and training-induced neuromotor adaptations in humans. The effect of applying tVNS concurrently to visuomotor training will be investigated by comparing the changes in central norepinephrine and changes in the visuomotor skill and corticospinal excitability due to training with and without tVNS (sham) in non-disabled humans. The visuomotor skill will be assessed with the root-mean-square error of the produced force against the target force, which will be normalized to the maximal voluntary contraction force (MVC) . The investigators expect that subjects with concurrent tVNS during training show greater increases in the visuomotor skill and corticospinal excitability after training. The investigators also expect that tVNS increases central norepinephrine, and the amount of neuromotor adaptations due to training is associated with that of tVNS-induced increase in central norepinephrine. These expected findings will be the first evidence on the efficacy of concurrent tVNS with motor training for upregulating central norepinephrine and facilitating training-induced neuromotor adaptations in humans. They will open new scientific and clinical fields of study that will lead to the creation of motor rehabilitation paired with tVNS that can enhance rehabilitation outcomes in individuals with motor impairment. Demonstration of associated changes between central norepinephrine and neuromotor adaptations due to tVNS in non-disabled humans is a necessary step for applying tVNS to rehabilitation with the understanding of the underlying mechanism and for potentially using central norepinephrine as a predictor of tVNS efficacy in rehabilitation.
- Conditions
- Healthy Young Adults
- Being tested
- tVNS, Motor training
- Keywords
- tVNS, training, neuromotor adaptation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tVNSOther
Intervention
Motor trainingOther
Same finger training for both arms
| Study group | Role | What they receive |
|---|---|---|
| Sham-tVNS to ear lobe | Sham comparator | Sham-tVNS will be applied to the ear lobe. Receives: Other: tVNS; Other: Motor training |
| tVNS to tragus | Active comparator | tVNS will be applied to the tragus. Receives: Other: tVNS; Other: Motor training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visuomotor Skill
Visuomotor skill was assessed with the amount of force error against the target trajectory. In the visuomotor task, subjects produced finger force against a force transducer to match a target trajectory as close as possible. The target was made of three low-frequency sinusoids with each sinusoid at different frequencies and amplitudes. This pattern spanned 20 s. The data in the middle 16 s were used for data analysis. For determining the visuomotor skill, the deviation of produced force from the target trajectory was calculated as the root-mean-square error. In this calculation, the difference between the target and produced force at each sampling point was squared, the squared values were summed across sampling points, and the squared root value of the summed value was determined and normalized to the maximal voluntary contraction (MVC) force. The data were expressed as the ratio of the baseline value (no unit). A lower value is considered a better outcome.
Measured: Day 1 (Baseline), Day 2 - 4, and Day 5 (Post)
Brain Excitability (MEP Amplitude)
Brain excitability was assessed with motor evoked potential (MEP) amplitude of the resting first dorsal interosseus muscles as resting corticospinal excitability. Surface EMG electrodes were attached over the muscle in a belly-tendon configuration. Subjects received single-pulse TMS to evoke MEP in the muscle. MEP was obtained from the surface EMG using a high-gain EMG preamplifier. Peak-to-peak- amplitude of MEP in response to TMS were averaged across the intensities of 115-160% relative to the resting motor threshold. Additionally, maximal M-wave amplitude was obtained by stimulating the ulnar nerve that innervates the muscle. MEP amplitude was normalized to the maximal M-wave amplitude of the muscle, so it was expressed in % of maximal M-wave. A higher value is considered higher brain excitability and a better outcome.
Measured: Day 1 (Baseline) and Day 5 (Post)
Salivary Amylase Activity
Central noradrenaline was assessed indirectly with salivary amylase activity. Saliva was sampled via salivette strips in the resting state before and after the training. Subjects were seated and rested for 5 minutes before sampling the samples. Collected saliva samples were immediately analyzed by using a dry-chemistry system automatically. Three saliva samples were analyzed and averaged across samples. Salivary amylase activity was measured and expressed in kU/I (kilo units per liter).
Measured: Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2018
- Study start20 May 2019
- Primary completion28 Jun 2021
- Study completion28 Jun 2021
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 Healthy Young AdultsStudies of the same condition, open and under way.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgia Institute of Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Minoru Shinohara, PhD, Principal investigator, Georgia Institute of Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03628976
- Sponsor's protocol ID
- H18151
- Other IDs
- 1R03NS106088-01A1
- Status last verified
- Aug 2022
- First submitted
- 8 Aug 2018
- Last updated
- 29 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Noninvasive Vagus Nerve Stimulation (VNS) for Neuromotor Adaptations
- ClinicalTrials.gov ID
- NCT03628976
- Acronym / sponsor ID
- H18151
- Conditions
- Healthy Young Adults
- Keywords
- tVNS, training, neuromotor adaptation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Georgia Institute of TechnologyUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 20 May 2019 (actual)
- Primary completion
- 28 Jun 2021 (actual)
- Study completion
- 28 Jun 2021 (actual)
- First posted
- 14 Aug 2018 (actual)
- Results
- Posted 19 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will examine how electrical stimulation of vagus nerve (i.e. nerve around the outer ear) from the skin surface during motor training influences a brain hormone (called norepinephrine), brain activity, and motor performance.
Detailed description
Motor function is compromised with advanced age, and motor impairment is involved in various neuromotor injuries and disorders including stroke, spinal cord injury, amputation, and aging. Development of effective interventions for facilitating neuromotor adaptation is essential for accelerating or augmenting rehabilitation outcomes in the control of impaired limbs. The ultimate goal of the study is to find non-pharmacological and non-invasive neuromodulating interventions for enhancing the rehabilitation outcomes that may be applied to individuals with impaired motor function. In rats, implanted afferent vagus nerve stimulation paired with motor training enhanced neuromotor adaptation and motor recovery most likely through increased release of central neuromodulators that originate from the brainstem. The investigators propose to translate the findings in rats into humans by applying vagus nerve stimulation noninvasively. Transcutaneous VNS (tVNS) can noninvasively activate the brainstem including locus coeruleus, where norepinephrine (i.e. neuromodulator) is synthesized. However, it is unknown whether tVNS leads to increasing neuromodulators and facilitating neuromotor adaptations when combined with motor training in humans. With potential applicability of this novel intervention for facilitating neuromotor adaptation to various clinical human populations in future scope, it is essential to start with the basic understanding about the effect of tVNS on the neuromotor system and training-induced adaptation in neuromotor behavior in non-disabled humans. The overarching hypothesis is that an application of tVNS increases central norepinephrine and facilitates training-induced neuromotor adaptations in humans. The specific aim is to examine the effect of tVNS on central norepinephrine and training-induced neuromotor adaptations in humans. The effect of applying tVNS concurrently to visuomotor training will be investigated by comparing the changes in central norepinephrine and changes in the visuomotor skill and corticospinal excitability due to training with and without tVNS (sham) in non-disabled humans. The visuomotor skill will be assessed with the root-mean-square error of the produced force against the target force, which will be normalized to the maximal voluntary contraction force (MVC) . The investigators expect that subjects with concurrent tVNS during training show greater increases in the visuomotor skill and corticospinal excitability after training. The investigators also expect that tVNS increases central norepinephrine, and the amount of neuromotor adaptations due to training is associated with that of tVNS-induced increase in central norepinephrine. These expected findings will be the first evidence on the efficacy of concurrent tVNS with motor training for upregulating central norepinephrine and facilitating training-induced neuromotor adaptations in humans. They will open new scientific and clinical fields of study that will lead to the creation of motor rehabilitation paired with tVNS that can enhance rehabilitation outcomes in individuals with motor impairment. Demonstration of associated changes between central norepinephrine and neuromotor adaptations due to tVNS in non-disabled humans is a necessary step for applying tVNS to rehabilitation with the understanding of the underlying mechanism and for potentially using central norepinephrine as a predictor of tVNS efficacy in rehabilitation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham-tVNS to ear lobe | Sham comparator | Other: tVNS, Other: Motor trainingSham-tVNS will be applied to the ear lobe. |
| tVNS to tragus | Active comparator | Other: tVNS, Other: Motor trainingtVNS will be applied to the tragus. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Men and women in the age range of 18-39 years will be recruited. All subjects will be healthy and right-handed. Subjects will match the ethnic distribution in the local community.
Key exclusion criteria (25 listed)
- To ensure the safety associated with TMS and transcutaneous afferent vagus nerve stimulation, following adults will be excluded as in our previous studies (Buharin et al. 2013, 2014) and following the standard recommendations (Keel et al. 2001):
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 |
|---|---|---|
| tVNSIntervention | Other | Sham-tVNS to ear lobe, tVNS to tragus |
| Motor trainingSame finger training for both arms | Other | Sham-tVNS to ear lobe, tVNS to tragus |
Primary outcome
Visuomotor Skill
Time frame: Day 1 (Baseline), Day 2 - 4, and Day 5 (Post)
Visuomotor skill was assessed with the amount of force error against the target trajectory. In the visuomotor task, subjects produced finger force against a force transducer to match a target trajectory as close as possible. The target was made of three low-frequency sinusoids with each sinusoid at different frequencies and amplitudes. This pattern spanned 20 s. The data in the middle 16 s were used for data analysis. For determining the visuomotor skill, the deviation of produced force from the target trajectory was calculated as the root-mean-square error. In this calculation, the difference between the target and produced force at each sampling point was squared, the squared values were summed across sampling points, and the squared root value of the summed value was determined and normalized to the maximal voluntary contraction (MVC) force. The data were expressed as the ratio of the baseline value (no unit). A lower value is considered a better outcome.
Brain Excitability (MEP Amplitude)
Time frame: Day 1 (Baseline) and Day 5 (Post)
Brain excitability was assessed with motor evoked potential (MEP) amplitude of the resting first dorsal interosseus muscles as resting corticospinal excitability. Surface EMG electrodes were attached over the muscle in a belly-tendon configuration. Subjects received single-pulse TMS to evoke MEP in the muscle. MEP was obtained from the surface EMG using a high-gain EMG preamplifier. Peak-to-peak- amplitude of MEP in response to TMS were averaged across the intensities of 115-160% relative to the resting motor threshold. Additionally, maximal M-wave amplitude was obtained by stimulating the ulnar nerve that innervates the muscle. MEP amplitude was normalized to the maximal M-wave amplitude of the muscle, so it was expressed in % of maximal M-wave. A higher value is considered higher brain excitability and a better outcome.
Salivary Amylase Activity
Time frame: Day 3
Central noradrenaline was assessed indirectly with salivary amylase activity. Saliva was sampled via salivette strips in the resting state before and after the training. Subjects were seated and rested for 5 minutes before sampling the samples. Collected saliva samples were immediately analyzed by using a dry-chemistry system automatically. Three saliva samples were analyzed and averaged across samples. Salivary amylase activity was measured and expressed in kU/I (kilo units per liter).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- 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.
Minoru Shinohara, PhD principal investigator
Georgia Institute of Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tVNS and Motor training in people with Healthy Young Adults, run by Georgia Institute of Technology at 1 site 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 25 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 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 19 Sep 2022). 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?
Visuomotor Skill (time frame: Day 1 (Baseline), Day 2 - 4, and Day 5 (Post)). The study lists 3 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 29 Sep 2022; AzTrials last refreshed its copy on 7 Nov 2026.