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The Effect of Deep Breathing and Transcutaneus Electrical Nerve Stimulation on Heart Rate Variability

Primary Purpose

Rheumatoid Arthritis, Systemic Lupus Erythematosus, Healthy Participants

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Non-invasive auricular electrical transcutaneous vagus nerve stimulation
Deep breathing
Sponsored by
Aalborg University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Rheumatoid Arthritis focused on measuring Heart rate variability, Deep breathing, Transcutaneous vagus nerve stimulation, Vagus nerve stimulation, Breathing exercises

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Men and women in the age range from 18 years to 85 years old.
  • For subproject 1 and 3 the participants must be diagnosed with either rheumatoid arthritis or systemic lupus erythematosus.
  • Must sign and date informed consent.

Exclusion Criteria:

  • Lacking ability to make or understand informed consent.
  • Medical history with psychiatric or psychological conditions which the person in charge of the research estimates will affect the participants ability to participate in the study.
  • Furthermore participants with severe mental illness will be excluded due to the fact that severe mental illness cause decreased heart rate variability.
  • Pregnancy.
  • Addict or prior addict defined as abuse of hash, opioids or other euphoriant drugs.
  • Known atrial fibrillation or atrial flutter.
  • Known chronic lung disease.

Sites / Locations

  • Aalborg UniversitetshospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deep breathing

Arm Description

Sub-project 1: To compare the effect of one session of DB and one session of non-invasive auricular tVNS on vagal nerve tone measured by HRV in healthy participants and in patients with RA and SLE. Sub-project 2: A dose-response study in healthy participants comparing the effect of 5, 15 and 30 minutes of DB on HRV. Sub-project 3: To investigate the effect of the optimal dose found in sub-project 2 in patients with RA and SLE measured by HRV, and to investigate its reproducibility by doing it twice.

Outcomes

Primary Outcome Measures

Heart rate variability root mean square of successive R-R intervals (RMSSD)
Heart rate variability is used as a surrogate measure of vagus nerve activity. The primary outcome is changes in the HRV-parameter RMSSD

Secondary Outcome Measures

Heart rate variability standard deviation of the R-R intervals (SDNN) and pairs of successive R-R intervals that differ more than 50 milliseconds divided by the total number of R-R intervals (PNN50)
Heart rate variability is used as a surrogate measure of vagus nerve activity - change in PNN50, SDNN

Full Information

First Posted
November 2, 2021
Last Updated
December 12, 2021
Sponsor
Aalborg University Hospital
Collaborators
Aalborg University
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1. Study Identification

Unique Protocol Identification Number
NCT05157334
Brief Title
The Effect of Deep Breathing and Transcutaneus Electrical Nerve Stimulation on Heart Rate Variability
Official Title
Can Manipulation of the Vagus Nerve Through Deep Breathing and Transcutaneus Electrical Nerve Stimulation Modulate Heart Rate Variability?
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
September 2022 (Anticipated)
Study Completion Date
September 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aalborg University Hospital
Collaborators
Aalborg University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This interventional study aims to investigate the effect of deep breathing (DB) and transcutaneous electrical vagus nerve stimulation (tVNS) on heart rate variability (HRV) in healthy participants and patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). HRV is used as a surrogate measure of vagal nerve tone. The study consists of three sub-projects: Sub-project 1: To compare the effect of one session of DB and one session of non-invasive auricular tVNS on vagal nerve tone measured by HRV in healthy participants and in patients with RA and SLE. The hypotheses is that DB has a similar effect on HRV as non-invasive electrical tVNS. Sub-project 2: A dose-response study in healthy participants comparing the effect of 5, 15 and 30 minutes of DB on HRV. The hypothesis was that HRV increases as a function of the number of minutes the DB is performed in healthy participants. Sub-project 3: To investigate the effect of the optimal dose found in sub-project 2 in patients with RA and SLE measured by HRV, and to investigate its reproducibility by doing it twice.The hypothesis was that HRV increases after DB in patients with RA and SLE, and the effect is reproducible. In all three sub-projects the washout period will be investigated by measuring HRV three times after the intervention. We hypothesise that the effect of DB and tVNS on HRV decreases over time.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis, Systemic Lupus Erythematosus, Healthy Participants
Keywords
Heart rate variability, Deep breathing, Transcutaneous vagus nerve stimulation, Vagus nerve stimulation, Breathing exercises

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
Sub-project 1: Randomized crossover study Sub-project 2: Randomized parallel Sub-project 3: Single groupe
Masking
None (Open Label)
Allocation
N/A
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Deep breathing
Arm Type
Experimental
Arm Description
Sub-project 1: To compare the effect of one session of DB and one session of non-invasive auricular tVNS on vagal nerve tone measured by HRV in healthy participants and in patients with RA and SLE. Sub-project 2: A dose-response study in healthy participants comparing the effect of 5, 15 and 30 minutes of DB on HRV. Sub-project 3: To investigate the effect of the optimal dose found in sub-project 2 in patients with RA and SLE measured by HRV, and to investigate its reproducibility by doing it twice.
Intervention Type
Device
Intervention Name(s)
Non-invasive auricular electrical transcutaneous vagus nerve stimulation
Intervention Description
A NEMOS ® stimulator (Cerbomed, Erlangen, Germany) is used for transcutaneous auricular vagus nerve stimulation. This is a handheld battery driven stimulator which stimulates conca in the outer ear. It stimulates in a serie of small electrical impulses with a pulse width at 250 us and a frequency at 25 Hz for 30 minutes in a cycle for 30 seconds "on" and 30 seconds "off" to avoid habituation. It is previously indicated that a stimulation intensity at 0,5 mA, 1 mA or 1,5 mA does not cause a significant chance in HRV, thus 0,5 mA is used in this study.
Intervention Type
Other
Intervention Name(s)
Deep breathing
Intervention Description
The participant is first verbally introduced to the breathing exercises, and then to the visually cue (animation), which the participant have to follow throughout the session.
Primary Outcome Measure Information:
Title
Heart rate variability root mean square of successive R-R intervals (RMSSD)
Description
Heart rate variability is used as a surrogate measure of vagus nerve activity. The primary outcome is changes in the HRV-parameter RMSSD
Time Frame
HRV is measured with five ECG recordings, each lasting 5 min. Two measurements with 5 minutes apart are made just prior to the 30 minutes of deep breathing/tvns. Three measurements are made after the intervention, separated by 7,5 minutes each.
Secondary Outcome Measure Information:
Title
Heart rate variability standard deviation of the R-R intervals (SDNN) and pairs of successive R-R intervals that differ more than 50 milliseconds divided by the total number of R-R intervals (PNN50)
Description
Heart rate variability is used as a surrogate measure of vagus nerve activity - change in PNN50, SDNN
Time Frame
HRV is measured before and after 30 minutes of deep breathing/tvns.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Men and women in the age range from 18 years to 85 years old. For subproject 1 and 3 the participants must be diagnosed with either rheumatoid arthritis or systemic lupus erythematosus. Must sign and date informed consent. Exclusion Criteria: Lacking ability to make or understand informed consent. Medical history with psychiatric or psychological conditions which the person in charge of the research estimates will affect the participants ability to participate in the study. Furthermore participants with severe mental illness will be excluded due to the fact that severe mental illness cause decreased heart rate variability. Pregnancy. Addict or prior addict defined as abuse of hash, opioids or other euphoriant drugs. Known atrial fibrillation or atrial flutter. Known chronic lung disease.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Salome Kristensen, MD, PhD
Phone
+ 45 99 32 81 83
Email
sakr@rn.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Salome Kristensen, MD, PhD
Organizational Affiliation
Aalborg University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aalborg Universitetshospital
City
Aalborg
State/Province
Region Nordjylland
ZIP/Postal Code
9000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salome Kristensen, MD, PhD
Phone
+ 45 99 32 81 83
Email
sakr@rn.dk

12. IPD Sharing Statement

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The Effect of Deep Breathing and Transcutaneus Electrical Nerve Stimulation on Heart Rate Variability

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