Rheumatoid ArthritisNCT05157334
The Effect of Deep Breathing and Transcutaneus Electrical Nerve Stimulation on Heart Rate Variability
A study testing Non-invasive auricular electrical transcutaneous vagus nerve stimulation and Deep breathing in people with Rheumatoid Arthritis and Systemic Lupus Erythematosus, run by Aalborg University Hospital at 1 site in Denmark.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis, Systemic Lupus Erythematosus, Healthy Participants
- What is being tested?
- Non-invasive auricular electrical transcutaneous vagus nerve stimulation and Deep breathing
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2021to Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Aalborg Universitetshospital
Aalborg, North Denmark, 9000
Salome Kristensen, MD, PhD, + 45 99 32 81 83, sakr@rn.dk
About this study
Official title: Can Manipulation of the Vagus Nerve Through Deep Breathing and Transcutaneus Electrical Nerve Stimulation Modulate Heart Rate Variability?
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:
Read more
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.
- Being tested
- Non-invasive auricular electrical transcutaneous vagus nerve stimulation, Deep breathing
- Keywords
- Heart rate variability, Deep breathing, Transcutaneous vagus nerve stimulation, Vagus nerve stimulation, Breathing exercises
- Medical subject headings
- Arthritis, Rheumatoid, Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-invasive auricular electrical transcutaneous vagus nerve stimulationDevice
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.
Deep breathingOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Deep breathing | Experimental | 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. Receives: Device: Non-invasive auricular electrical transcutaneous vagus nerve stimulation; Other: Deep breathing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 outcomes (1)
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
Measured: HRV is measured before and after 30 minutes of deep breathing/tvns.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2021
- Study start1 Sep 2021
- Primary completionSep 2022 (estimated)
- Study completionSep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Aalborg University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Sub-project 1: Randomized crossover study Sub-project 2: Randomized parallel Sub-project 3: Single groupe
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Aalborg University
- Responsible party
- Principal investigator, Salome Kristensen, Aalborg University Hospital
- Investigators
- Salome Kristensen, MD, PhD, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05157334
- Sponsor's protocol ID
- N-20210002
- Status last verified
- Dec 2021
- First submitted
- 2 Nov 2021
- Last updated
- 15 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Manipulation of the Vagus Nerve Through Deep Breathing and Transcutaneus Electrical Nerve Stimulation Modulate Heart Rate Variability?
- ClinicalTrials.gov ID
- NCT05157334
- Acronym / sponsor ID
- N-20210002
- Keywords
- Heart rate variability, Deep breathing, Transcutaneous vagus nerve stimulation, Vagus nerve stimulation, Breathing exercises
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Collaborators
- Aalborg University
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- Sep 2022 (estimated)
- Study completion
- Sep 2022 (estimated)
- First posted
- 15 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Sub-project 1: Randomized crossover study Sub-project 2: Randomized parallel Sub-project 3: Single groupe
| Arm | Type | Receives |
|---|---|---|
| Deep breathing | Experimental | Device: Non-invasive auricular electrical transcutaneous vagus nerve stimulation, Other: Deep breathingSub-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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-invasive auricular electrical transcutaneous vagus nerve stimulationA 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. | Device | Deep breathing |
| Deep breathingThe 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. | Other | Deep breathing |
Primary outcome
Heart rate variability root mean square of successive R-R intervals (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.
Heart rate variability is used as a surrogate measure of vagus nerve activity. The primary outcome is changes in the HRV-parameter RMSSD
1 secondary outcome
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)
Time frame: HRV is measured before and after 30 minutes of deep breathing/tvns.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salome Kristensen, MD, PhD principal investigator
Aalborg University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Non-invasive auricular electrical transcutaneous vagus nerve stimulation and Deep breathing in people with Rheumatoid Arthritis and Systemic Lupus Erythematosus, run by Aalborg University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Salome Kristensen, MD, PhD (+ 45 99 32 81 83, sakr@rn.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate variability root mean square of successive R-R intervals (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2021.