Clinical trial NCT06294509: TaVNS Application Timing During Robotic Sensorimotor Task
Official title: Feasibility and Effects of Transcutaneous Auricular Vagus Nerve Stimulation Timings in a Sensorimotor Task
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Healthy
Keywords: sensorimotor adaptation
motor learning
transcutaneous auricular Vagus nerve stimulation
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
First posted: 2024-03-05
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-blinded, pseudo-randomised, exploratory, single-centre, national, longitudinal study
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial is to evaluate the feasibility and effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) in enhancing sensorimotor learning and adaptation. This study will focus on healthy individuals performing a robotic sensorimotor task.

Main Questions it Aims to Answer:

How does taVNS, with different timing protocols, affect the feasibility and effectiveness of performing a robotic sensorimotor task? What is the impact of taVNS on sensorimotor learning and adaptation?

Participants Will:

Be pseudo-randomly assigned to one of five experimental groups with different taVNS stimulation timings.

Perform a sensorimotor task multiple times across sessions, spanning a maximum of two weeks or until achieving 70% accuracy in two successive sessions.

Have kinematic data collected by a robot during the task. Have physiological data measured using external sensors. Fill out questionnaires about the feasibility of taVNS and other subjective measures after each session.

Comparison Group:

Researchers will compare the four experimental groups to each other to see if different taVNS stimulation timings affect sensorimotor learning outcomes, as well as to a control group that will receive no stimulation.

Detailed description: Overview:

This study focuses on the potential of transcutaneous auricular Vagus Nerve Stimulation (taVNS) in motor neurorehabilitation for conditions like Parkinson's disease, traumatic brain injury, spinal cord injury, and stroke. taVNS, approved for various neurological conditions and known for its safety, activates neuromodulators contributing to plasticity and motor learning. However, the optimal stimulation parameters, especially timing during movement, are not fully explored.

Study Goals:

Primary Objective: To assess the feasibility and effects of different taVNS timing protocols in a robotic sensorimotor task on sensorimotor learning and adaptation. The hypothesis is that varying taVNS-movement timings will influence both subjective and objective feasibility measures and sensorimotor adaptation.

Secondary Objectives: To compare movement kinematics and contrast perceived stimulation effects with measured physiological outcomes and task performance metrics.

Methodology:

The study will be conducted at Swiss Federal Institute of Technology (ETH) Zurich with healthy subjects using a robotic sensorimotor task to evaluate the feasibility of movement-timed taVNS and its influence on learning new sensorimotor skills.

Participants will be assigned different stimulation timings, with the study assessing motor learning and performance consistency across a maximum of 6 sessions or until 70% success is reached in two successive sessions.

The study design is single-blinded, pseudo-randomized, exploratory, and longitudinal, employing controls like no stimulation and randomly-timed stimulation.

Intervention Details:

Before each session, two electrodes (e.g. TensCare pads) will be connected to the pulse generator and 1) placed on the cymbae conchae of the ear and 2) on the tragus of the ear, allowing for a previously described taVNS biphasic pulse train to travel. Here, biphasic square pulses of 250ms width are sent at 25 Hertz (Hz) frequency for 0.5s at a maximum aptitude of 3 milliamperes (mA). The stimulation pulses are current-controlled, limited to 50 Volts (V) and regulated by a pulse generator that limits deliverable current in hardware by design with serial resistors and diodes.

At the start of the session, participants will use a python graphical user interface (GUI) to calibrate the desired taVNS amplitude by gradually increasing it from minimal 0.1 mA up to the maximal tolerated amplitude below 3 mA in the intervals of 0.1 mA. The level of intensity will be set to 90% of the maximally tolerated amplitude for the person (typical \~1.5-2 mA \& limited to 3mA, which is significantly below the safety limit of 50mA (according to the Product Safety Standards for Medical Devices, IEC 60601-2-10:2012). This procedure takes 1-2 min. Following the calibration, the session with the sensorimotor task will begin.

Sensorimotor task The sensorimotor task utilizes a commercial haptic end effector (Touch, 3D systems), a custom made 3D printed handle and a virtual reality environment, implemented in python and PsychoPy software on a Microsoft Windows laptop. The robotic manipulandum is synchronized to a 1cm circular cursor in the workspace of the virtual environment. Additionally, an arm-support (SaeboMas Mini) is used to support the arm against gravity to reduce fatigue and keep the arm in the correct position - elbow is 90 degrees perpendicular to the ground.

The goal of the sensorimotor task is to reach a 2.4cm target at a distance of 10 cm away from a starting position, both visually represented in the virtual environment. In order to successfully complete a trial the participant must reach the target within a time constraint of 0.5 s +/- 0.067 s. There will be a 0.5 s tone sound notifying the target duration of the movement. During this movement the cursor position is hidden and not displayed on the screen (in perturbation and retention phases) in order to force feedforward motor adaptation, rather than visually-guided feedback control, as feedforward adaptation may be impaired in stroke patients. Results of each trial are displayed as 3 distinct possibilities - correct, target reached too quickly, or target not reached. The subject will be notified of the outcome of the trial by the target turning either, green, orange or red respectively. Afterwards the start location will be displayed for the participant to return to. After 1-3 s within the starting point a new trial will be initiated.

Participants will perform 75 baseline trials (no visuomotor rotation) to get familiar with the robotic manipulandum and the environment. Then participants will perform an additional 150 trials in the challenged condition with a virtual rotational field (visuomotor rotation/perturbation), displayed on the screen. Subjects will not be informed about the nature of the sensorimotor challenge and will have to progressively learn the corrective mapping to adapt to the perturbation. No external forces will be applied and the haptic end-effector is solely used to measure handle end-point kinematics. Then subjects will perform 50 trials of the same baseline trials (wash-out) and finally 50 more trials of the rotational field (retention). The time requirement is expected to be 5-10 min for the setup and explanations and \~30 min for the sensorimotor task. Data from each trial will be stored containing the position of the cursor, success/fail and time information for subsequent analysis. Additional movement kinematic data may be collected using inertial measurement unit (IMU) sensors worn on the wrist. The IMU records acceleration and gyroscope measurements and logs data to the experimental computer at a rate of 120Hz. Additionally all data pertaining to stimulation will be stored, this includes timing, impedance measurements and all communication commands to and from the stimulator.

Research Significance:

The findings could inform future clinical studies in neurorehabilitation. The study uses a "Touch™" haptic device for the task, ensuring participant safety and comfort.

Potential side effects of taVNS are minimal and closely monitored.

Eligibility criteria: Inclusion Criteria:

* Healthy participants above 18 years of age and able to provide informed consent and understand the study requirements

Exclusion Criteria:

* Individuals with major untreated depression, major cognitive and/or communication deficits, and major comprehension and/or memory deficits that may interfere with the informed consent process, task-specific practice, or communication of adverse events will be excluded from the study.
* Neurological conditions such as epilepsy, participation in any other research trial, pregnancy, use of implanted electrical devices, and use of medication or procedure that interferes with vagal functions.
* Pregnancy or trying to get pregnant.

Primary outcomes:
measure: Subjectively perceived tolerance of taVNS and perceived difficulty of motor task
timeFrame: From enrollment to end of study at 2 weeks
measure: Success of the sensorimotor challenge
timeFrame: After the intervention
measure: Mean Change from Baseline in Galvanic Skin Response (GSR)
timeFrame: During and immediately after taVNS
measure: Mean Change from Baseline in Heart Rate (HR)
timeFrame: During and immediately after taVNS
measure: Mean Change from Baseline in Pupil Diameter (PD)
timeFrame: During and immediately after taVNS
measure: Mean Change from Baseline in electroencephalogram (EEG)
timeFrame: During and immediately after taVNS
Secondary outcomes:
measure: Subjectively perceived positive effects of taVNS on motor performance
timeFrame: After each session, from enrollment to end of treatment at 2 weeks
measure: Change of movement parameters from baseline
timeFrame: After each session, from enrollment to end of study at 2 weeks
measure: Associations between outcomes
timeFrame: upon completion of study, at 2 weeks
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: ETH Zurich
Study officials:
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