Noninvasive Vagus Nerve Stimulation (VNS) for Neuromotor Adaptations

NCT03628976 | Completed Results

• 2 other identifiers: H181511R03NS106088-01A1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Young Adults

Keywords

tVNS, training, neuromotor adaptation

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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).

  Day 3

Study Arms (2)

Sham-tVNS to ear lobe

SHAM COMPARATOR

Sham-tVNS will be applied to the ear lobe.

Other: tVNS; Other: Motor training

tVNS to tragus

ACTIVE COMPARATOR

tVNS will be applied to the tragus.

Other: tVNS; Other: Motor training

Interventions

tVNS OTHER

Intervention

Sham-tVNS to ear lobe; tVNS to tragus

Motor training OTHER

Same finger training for both arms

Sham-tVNS to ear lobe; tVNS to tragus

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Georgia Institute of Technology: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Human Neuromuscular Physiology Lab

Atlanta, Georgia, 30332, United States

Location

Results Point of Contact

• Title: Dr. Minoru Shinohara
• Organization: Georgia Institute of Technology

shinohara@gatech.edu

404-894-1030

Study Officials

• Minoru Shinohara, PhD

  Georgia Institute of Technology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 14, 2018
• Study Start: May 20, 2019
• Primary Completion: June 28, 2021
• Study Completion: June 28, 2021
• Last Updated: September 29, 2022
• Results First Posted: September 19, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)