Effects of Transcutaneous Electrical Stimulation on the Autonomous Nerve System in Healthy Young People

NCT05289817 | Completed

• 1 other identifier: 2020/011
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular disease is one of the most important causes of death and disability in the world. An autonomic imbalance is associated to cardiovascular risks and disorders. Electrical stimulation (ES) applied by surface electrodes is a non-invasive therapeutic approach with low side-effects. In the last years, some studies had investigated the effects of ES on the autonomic nervous system and cardiovascular system. However, different intensities, frequencies and electrode locations had been used, which makes difficult to clarify the optimal parameters. The aim of this study is to analyze the effects of ES on autonomic nervous modulation in healthy subjects comparing three different locations of application for ES. Participants will be aleatory assigned to one of three groups for a single-session of 20-minute transcutaneous ES: a) an auricular intermittent ES in an area that is believed to be connected to the vagal nerve (cymba conchae); b) an auricular sham intermittent ES, meaning a real ES but applied on an ear location not connected to the vagal nerve (scapha); and c) an upper back continuous ES (C7-T4), a placement that is thought to be connected to the stellate (sympathetic) ganglion. All the protocols will be stated at a non-painful intensity. After that, the hand grip exercise will be executed. The heart rate variability (HRV) and heart frequency (HR) will be measured in four main times: the baseline, in the final minutes of the ES, after the ES and after finishing the hand grip exercise. Blood pressure will be measured also at all the time points except during the ES due to the possibility of interferences. Adverse effects will be assessed after ES and 48 h later. The study will provide initial knowledge about how different electrical stimulation locations contribute to reduce sympathetic excitation and improve the sympathovagal balance.

Conditions

Healthy Volunteers; Cardiovascular System; Autonomic Nervous System

Keywords

Electric Stimulation Therapy; Transcutaneous Electric Nerve Stimulation; Parasympathetic Nervous System; Stellate Ganglion; Hearth Rate; Blood Pressure

Outcome Measures

Primary Outcomes (13)

• RR

  The time of RR intervals (ms) will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland). The mean values of RR intervals (ms) and the standard deviation of all RR intervals (ms) will be obtained.

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• RMSSD

  Root mean square of successive RR interval differences (ms). It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• pNN50

  Relative number of successive RR interval pairs that differ more than 50 ms (percentage). It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• HF

  High frequency refers to HRV frequency band (0.15-0.4 Hz). It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• LF

  Low frequency refers to HRV frequency band (0.04-0.15 Hz). It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• LF/HF

  The ratio of LF to HF power will be calculated along with normalised LF/HF where baseline values will set to 1. It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• SD1

  The poincaré plot short term variability (ms). It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• SD2

  The poincaré plot long term variability (ms). It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• SD2/SD1

  Poincaré plot long and short term variability ratio. It will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, During 20 minutes Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• Mean heart rate

  The mean frequency will be obtained from Polar S800 with Polar T31 transmitter (Polar Electro, Kempele, Finland), and it will be extracted with Kubios software (University of Eastern Finland, Kuopio, Finland).

  5 minutes before Electrical Stimulation, during 20 minutes of Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• Systolic blood pressure

  Blood pressure will be continuously acquired by SOMNOtouch NIBP (Somnomedics, GmbH, Randersacker, Germany) that is an ambulatory cuffless device for continuous (beat-to-beat), noninvasive BP monitoring. The system consists of a finger photoplethysmograph and three ECG leads, connected to a watch-like control unit placed at the wrist level and equipped with a screen where beat-to-beat pulse waveform, ECG, and PTT changes are displayed. All these measurements are unified to obtain systolic blood pressure in mmHg.

  5 minutes before Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• Diastolic blood pressure

  Blood pressure will be continuously acquired by SOMNOtouch NIBP (Somnomedics, GmbH, Randersacker, Germany) that is an ambulatory cuffless device for continuous (beat-to-beat), noninvasive BP monitoring. The system consists of a finger photoplethysmograph and three ECG leads, connected to a watch-like control unit placed at the wrist level and equipped with a screen where beat-to-beat pulse waveform, ECG, and PTT changes are displayed. All these measurements are unified to obtain the diastolic blood pressure in mmHg.

  5 minutes before Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

• Mean arterial pressure

  Blood pressure will be continuously acquired by SOMNOtouch NIBP (Somnomedics, GmbH, Randersacker, Germany) that is an ambulatory cuffless device for continuous (beat-to-beat), noninvasive BP monitoring. The system consists of a finger photoplethysmograph and three ECG leads, connected to a watch-like control unit placed at the wrist level and equipped with a screen where beat-to-beat pulse waveform, ECG, and PTT changes are displayed. All these measurements are unified to obtain the mean arterial pressure in mmHg.

  5 minutes before Electrical Stimulation, 5 minutes after Electrical Stimulation, During 3 minutes hand-grip exercise, 15 minutes after hand grip exercise

Secondary Outcomes (3)

• Electrical simulation tolerance

  20 minutes after initiating electrical stimulation

• Rating of perceived effort

  Immediately after the hand grip exercise

• Adverse effects

  At 20 minutes after initiating electrical stimulation and at 48 hours after the electrical stimulation

Other Outcomes (15)

• Blind outcome assessment

  15 minutes after the hand grip exercise

• Amplitude of electrical stimulation

  20 minutes of electrical stimulation

• Respiratory frate

  5 minutes before Electrical Stimulation, during 20 minutes of Electrical Stimulation, 5 minutes after Electrical Stimulation, 15 minutes after hand grip exercise

Study Arms (3)

Transcutaneous Vagus Electrical Nerve Stimulation (t-VNS)

EXPERIMENTAL

Transcutaneous electrical stimulation will be delivered by trains for twenty minutes to the right cymba conchae at the ear.

Device: Transcutaneous Vagus Nerve Stimulation (t-VNS)

Transcutaneous Sympathetic Ganglion Electrical Nerve Stimulation (t-SNS)

ACTIVE COMPARATOR

Transcutaneous electrical stimulation will be delivered continuously for twenty minutes to the cervicothoracic region.

Device: Transcutaneous Sympathetic Ganglion Electrical Stimulation (t-SES)

Sham Transcutaneous Vagus Electrical Nerve stimulation (sham t-VNS)

SHAM COMPARATOR

Transcutaneous electrical stimulation will be delivered by trains for twenty minutes to the right scapha at the ear.

Device: Sham Transcutaneous vagus nerve stimulation (Sham t-VNS)

Interventions

Transcutaneous Vagus Nerve Stimulation (t-VNS) DEVICE

Type of device and current: portable machine, low frequency current, constant current Type of wave: square biphasic pulses Pulse duration: 350 microseconds Frequency: 10 Hz Number of channels: one Location and electrodes: cymba conchae at right ear (vagus branch nerve area); a clip electrode will be applied with its cathode on anterior cymba conchae, the anode placed behind. Amplitude: from 2 times the perception threshold (individualized) at a comfortable, non-painful amplitude, and to a maximum of 9 mA. It will be increased, if necessary, each 5 minutes in order to maintain the same level of tingling sensation On-Off times: trains of 30 s on, 5 s rump up, 1 s rump down, 24 s off Duration: 20 minutes

Transcutaneous Vagus Electrical Nerve Stimulation (t-VNS)

Transcutaneous Sympathetic Ganglion Electrical Stimulation (t-SES) DEVICE

Type of device and current: portable machine, low frequency current, constant current Type of wave: square biphasic pulses Pulse duration: 350 microseconds Frequency: 5 Hz Number of channels: two Location and electrodes: cervicothoracic area (stellate ganglion region); first channel: new 5 cm x 5 cm self-adhesive electrodes will be applied at 1-1.5 cm both sides of the vertebral spinous processes, approximately from C7 to T4, upper cathode on the left side of C7 and lower cathode on the right side. Amplitude: 2 mA above the muscle contraction threshold (individualized) at a comfortable, non-painful amplitude and to a maximum of 25 mA. It will be increased, if necessary, each 5 minutes in order to maintain the same level of muscle contraction On-Off times: no trains, continuously delivered Duration: 20 minutes

Transcutaneous Sympathetic Ganglion Electrical Nerve Stimulation (t-SNS)

Sham Transcutaneous vagus nerve stimulation (Sham t-VNS) DEVICE

Type of device and current: portable machine, low frequency current, constant current Type of wave: square biphasic pulses Pulse duration: 350 microseconds Frequency: 10 Hz Number of channels: one Location and electrodes: scapha at right ear (non vagus innervated region); a clip electrode will be applied with its cathode on anterior scapha, the anode placed behind. Amplitude: from 2 times above the perception threshold (individualized) at a comfortable, non-painful amplitude, and to a maximum of 9 mA. It will be increased, if necessary, each 5 minutes in order to maintain the same level of tingling sensation On-Off times: trains of 30 s on, 5 s rump up, 1 s rump down, 24 s off Duration: 20 minutes

Sham Transcutaneous Vagus Electrical Nerve stimulation (sham t-VNS)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• University students and academic or administrative staff, non smokers, self-perceived as healthy

You may not qualify if:

• No history of neurological, neurosurgical, psychiatric, cardiological disease, pulmonary disease, syncope, seizure, head trauma, cranial or neck surgery, aneurisms, or any condition or treatment which could affect the functioning of the autonomous nerve system or the cardiovascular system (by self-report).
• BMI of 30 or over
• High blood pressure (systolic blood pressure of 140 mmHg or over, or diastolic blood pressure of 90 mmHg or over)
• Spontaneous respiratory rate under 10 breaths per minute
• Professional athletes
• Inability to reach the minimum amplitude required during electrical stimulation
• Any arm or hand pain (dominant side)
• Any contraindication for electrical stimulation (pregnancy or risk or being pregnant, any implanted electronical device, irritation or pain at the skin location for the electrodes, intolerance to electrical stimulation) or any condition which could affect the placement of the electrodes or the perception of the electrical stimulus.

Sponsors & Collaborators

• Universidade da Coruña: lead

Study Sites (1)

Universidade da Coruna

A Coruña, 15006, Spain

Location

Study Officials

• Alicia Martínez-Rodríguez, PhD

  Universidade da Coruña (UDC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Allocation concealment, stratified by sex, will be ensured by the use of sealed envelopes containing the treatment allocation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer, PhD, MSC, PT. Faculty of Physical Therapy.

Model Details: The study is a prospective, randomized, three-armed, sham-controlled, single-blind, exploratory clinical trial in healthy subjects

Study Record Dates

• First Submitted: February 10, 2022
• First Posted: March 21, 2022
• Study Start: March 22, 2022
• Primary Completion: June 27, 2022
• Study Completion: June 29, 2022
• Last Updated: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)