Effects of Transcutaneous Vagus Nerve Stimulation in Older Adults

N/AEnrolling By InvitationNCT07292623

Universidade da Coruña12 enrolled

Overview

The autonomic nervous system consists of two branches, the sympathetic and the parasympathetic, which must work in balance. Its functioning can be measured indirectly by heart rate variability, which is the time between heartbeats, which is not constant. The more it varies, the greater the role of the parasympathetic branch, and vice versa. However, with age, an imbalance can occur and the parasympathetic branch can play a lesser role, resulting in less heart rate variability (the times between heartbeats become more similar). The aim of this study is to know if electrical stimulation in the ear can improve the balance between the two branches of the autonomic nervous system in older adults, comparing two different locations of application. The main questions to answer are: Does applying electrical stimulation to a specific area of the ear improve the balance of the autonomic nervous system? Does it also help improve hand tremors, balance, concentration, saliva production, and voice quality?

Electrical stimulation (ES) of the nervous system, also denominated as neuromodulation, has been investigated for diverse conditions as cardiovascular diseases, chronic pain and psychiatric conditions. It is unknown which locations and parameters can be more effective and better tolerated. The transcutaneous ES is a non-invasive technique which has fewer side-effects than subcutaneous vagus nerve stimulation. The aim of this study is to analyze the acute effects of transcutaneous ES on autonomic nervous modulation by heart rate variability (HRV) and heart frequency (HF) in older adults who perceive themselves as healthy, comparing two different locations for the ES, before and after a battery of motor, cognitive and other tests.. In addition, the tolerance to the current and the side-effects will be compared. Once the participants have given their informed consent and had been checked for exclusion criteria, are invited to an experimental session. Subjects will be advised to refrain from caffeine or alcohol for 12 h and vigorous exercise for at least 24h prior to the intervention. The volunteers will be randomized by sex to begin with one of two electrode locations: cymba concha and cavum concha at the left ear (active session); or scapha and lobule at the left ear (sham-session). These two interventions will be denominated as Transcutaneous Vagus Electrical Nerve Stimulation (t-VNS) and Sham Transcutaneous Vagus Electrical Nerve Stimulation (sham t-VNS). Allocation concealment, stratified by sex, will be ensured as the person will choose a piece of paper with the assignment coded with numbers (real/placebo) from a bag containing all the coded options that only the person applying the stimulation will see and understand (coded) The stimulation location will be wiped down with alcohol and the minimum intensity, at which the stimulus is perceived, will be registered. Subsequently, the intensity will be increased until reaching the discomfort threshold, and then decreased to a strong but well-tolerated sensation. At the beginning of the intervention, the different tests will be explained to the participant, the chest strap will be placed, its synchronisation with the HRV measurement system will be checked, and the TENS equipment will be placed on the waist using a belt. After 10 minutes, the pre-stimulation assessment will be carried out. At the beginning of each session, participants will be allowed to try each one to familiarise themselves with it. At the end of the session, the stimulation will be applied and the variables will be measured in the same order during the actual electrical stimulation or placebo, as appropriate. The second session will be performed in the same way, but using the application not used in the previous session (placebo or active, as appropriate). The participants will be asked upon completion of the session their presumed group assignment. Adverse effects will be checked at the end of each session, and again 48 h after.

Interventions

Active location tVNSDEVICE

The tVNS will be performed at 20 Hz and 200 microseconds, in the area innervated by the auricular branch of the vagus nerve (cymba concha and concha) in the active location. The intensity will be set above the sensory threshold (intense tingling sensation) but below the level of discomfort. The TENS will be set to 27 seconds of working time, with a 3-second ramp-up and 90 seconds off. It will last until the end of the last HRV test.

Sham ComparatorDEVICE

The tVNS will be performed at 20 Hz and 200 microseconds, in the area not innervated by by the auricular branch of the vagus nerve (scapha) for sham TENS. The intensity will be set above the sensory threshold (intense tingling sensation) but below the level of discomfort. The TENS will be set to 27 seconds of working time, with a 3-second ramp-up and 90 seconds off. It will last until the end of the last HRV test.

Eligibility

Sex: ALLMin age: 65 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Non-smokers aged 65 to 80, with BMI from 18.5 to less than 30, who consider themselves healthy and are able to maintain their balance for at least 1 minute without assistance, living in A Coruña (Spain), with a 50% allocation to each sex Exclusion Criteria: * systolic blood pressure above 160 mm Hg and diastolic blood pressure above 100 mm Hg, * previous vagotomy, history of syncope in the last two years, or lack of reliable reading in heart rate variability * presence of chronic pain (migraine, back, neck, shoulder, etc.) or being diagnosed with or receiving treatment for malignant, cardiovascular disease (excluding hyperlipidaemia and hypercholesterolaemia), respiratory, neurological or autonomic, metabolic (e.g. diabetes), osteoarticular of autoimmune origin (e.g. arthritis), psychiatric or history of treatment with antidepressants or anxiolytics * impaired cognitive level * presence of any contraindication or difficulty in applying TENS: pacemaker, defibrillator or any implanted electronic device, apprehension of electric current, burns or irritated skin or allergic reaction or any alteration in the area that prevents the electrode from being placed on the left ear; * previous application of electrical stimulation to the ear

Outcomes

Primary Outcomes

HRV

Heart Rate Variability (HRV) using Kubios app and H10 polar heart rate monitor chest strap, in periods of 5 minutes: * Frequency domain; ratio LF/HF power will be calculated along with normalised LF/HF where baseline values will set to 1; Low frequency (LF, referred to HRV frequency band 0.04-0.15 Hz); High frequency (HF = HRV frequency band 0.15-0.4 Hz); absolute powers of LF, and HF bands (ms2); normalized power (powers of LF and HF bands in normalised units, %) * Time domain: RR (mean values of RR intervals in ms) ; SDNN (Standard deviation of RR intervals); RMSSD (Root mean square of successive RR interval differences, in ms) * Non-linear methods: the poincaré plot short term variability (SD1, ms); the poincaré plot long term variability (SD2, ms). * Global measures: Stress Index (SI), square root of Baevsky's stress index; Parasympathetic nervous system (PNS) index

Time frame: Change from pre-tVNS (baseline= post initial battery of tests, about minute 35 after initiating the session) and during tVNS (post second battery of tests, 5 minutes before the end of the session, about minute 70)

Secondary Outcomes

HRV

Heart Rate Variability (HRV) using Kubios app and H10 polar heart rate monitor chest strap in periods of 5 minutes: * Frequency domain; ratio LF/HF power will be calculated along with normalised LF/HF where baseline values will set to 1; Low frequency (LF, referred to HRV frequency band 0.04-0.15 Hz); High frequency (HF = HRV frequency band 0.15-0.4 Hz); absolute powers of LF, and HF bands (ms2); normalized power (powers of LF and HF bands in normalised units, %) * Time domain: RR (mean values of RR intervals in ms) ; SDNN (Standard deviation of RR intervals); RMSSD (Root mean square of successive RR interval differences, in ms) * Non-linear methods: the poincaré plot short term variability (SD1, ms); the poincaré plot long term variability (SD2, ms). * Global measures: Stress Index (SI), square root of Baevsky's stress index; Parasympathetic nervous system (PNS) index; Sympathetic nervous system (SNS) index * Mean heart rate (beats/min) * ECG derived respiration (breaths/min)

Time frame: Change from pre-tVNS (baseline = post initial battery of tests, about minute 35 after initiating the session) and initial tVNS (5 minutes after setting the intensity of tVNS, about 45 minutes after initiating the session)

Hand tremor

The tremor in both hands will be measured with the app (G-Sensor Logger) for a minute, using a mobile phone secured to each hand (both hands)

Time frame: Change from pre-tVNS (baseline= initial battery of tests, about minute 10 to 15 after initiating the session) and during tVNS (post = second battery of tests, about 50 to 55 minutes after after setting the intensity of tVNS)

Salive

To measure salivation, a dry cloth will be placed in the mouth and weighed after 2 minutes without swallowing to estimate the volume of saliva produced.

Time frame: Change from pre-tVNS (baseline= initial battery of tests, from minute 15 to 20 after initiating the session) and during tVNS (post second battery of tests, about 55 to 60 minutes after after setting the intensity of tVNS)

Flanker test

The Flanker test is designed to assess selective attention and inhibitory function, deciding the direction of a central row, flanked by nontarget stimuli, which can be congruent (matching the target) or incongruent (opposite to the target). It will be done with both arms.

Time frame: Change from pre-tVNS (baseline= initial battery of tests, about 20 minutes after initiating the session) and during tVNS (post second battery of tests = 60 minutes after initiating the session)

Balance test

For balance, a baropodometric platform will be used and the centre of pressure area (mm), the ellipse area (mm2), the speed (mm/s)and the displacements in the axes of space (mm) will be measured, with eyes open and eyes closed, twice on each occasion

Time frame: Change from pre-tVNS (baseline= post initial battery of tests, from minute 25) and during tVNS (post second battery of tests = from minute 65)

Voice

The PRAAT software will be used to test the voice twice, when sustaining till 10 seconds the vowel "a" and when reading a text at their usual volume. The intensity, the fundamental frequency (F0), the jitter and shimmer parameters and the HNR (Harmonic to Noise Ratio) will be measured

Time frame: Change from pre-tVNS (baseline= post initial battery of tests, from minute 35) and during tVNS (post second battery of tests = from minute 75 after initiating the session)

Tolerance

The level of tolerance of the entire stimulation (by electrical stimulation, by electrodes, or by both) will be measured on a VAS scale from 0 (no discomfort at all) to 10 (the discomfort would have prevented me from finishing the session)

Time frame: Immediately after the intervention (around the 80th minute after the start of the session)

Adverse effects

A questionnaire will be used to test the presence, severity, persistence and causality of ear pain, headache, tingling, itching, redness, irritation, pressure, dizziness, nausea, vertigo, fatigue, vertigo, palpitations, tinnitus, unpleasant feeling, other

Time frame: Immediately after the intervention, and after 48 hours of ending it