Atrial FibrillationLLT-SPANSNCT04682704
The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function
A study testing Parasym in people with Atrial Fibrillation and Heart Failure, Diastolic, run by University of Oklahoma at 1 site in United States.
Trial summary
Low level transcutaneous vagus nerve stimulation (LLTS) involves delivery of electrical impulses transcutaneously at the auricular branch of vagus nerve and it has been shown to have anti-inflammatory and anti-arrhythmic effects. Read more about this study
- Who is it for?
- Ages 21 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Atrial Fibrillation, Heart Failure, Diastolic
- What is being tested?
- Parasym
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2021to Feb 2025
- 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 21 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female patients older than 21 year old
- Healthy volunteers free from diagnosis of AF, heart failure, coronary artery disease or diseases that affect the autonomic nervous system.
- Patients with Paroxysmal Atrial Fibrillation
- Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)
Who cannot join
- Recent (<6 months) stroke
- Recent (<6 months) myocardial infarction
- Heart failure (NYHA class III or IV)
- Left ventricular ejection fraction <50%
- Recurrent vaso-vagal syncopal episodes
- Unilateral or bilateral vagotomy
Show all 11Show fewer
- Pregnancy or breast feeding
- Uncontrolled diabetes or hypertension
- Inability or unwillingness to understand and/or sign informed consent
- Any serious disease that affects autonomic nervous system function
- Any medications that affect autonomic nervous system function
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Brittany Karfonta, RN, 405-271-2229, brittany-karfonta@ouhsc.edu
Stavros Stavrakis, MD, PhD
About this study
Low level transcutaneous vagus nerve stimulation (LLTS) involves delivery of electrical impulses transcutaneously at the auricular branch of vagus nerve and it has been shown to have anti-inflammatory and anti-arrhythmic effects. In previous studies from our laboratory, we found that LLTS significantly suppressed atrial fibrillation (AF) inducibility and decreased AF duration. The anti-arrhythmic effects of LLTS were similar to those delivered to the cervical VN trunk. LLTS for just one hour significantly shortened the AF duration and decreased inflammatory cytokines. We have also shown that LLTS leads to favorable heart rate variability (HRV) changes and cardiac mechanics in patients with diastolic dysfunction. These results support the use of LLTS as a novel non-pharmacological, non-ablative treatment modality for AF and possibly other inflammatory conditions. However, the optimal stimulation parameters of LLTS remain to be determined.
In this study, we aim to examine the effect of 2 different frequencies (5Hz and 20Hz) and 2 different amplitudes (50% below the pain threshold and 1mA below the pain threshold) of LLTS on heart rate variability with deep breathing (HRVdb), mental arithmetic stress test (MAST), frequency domain measures of heart rate variability (HRV) and brain stem evoked potentials (BSEVP) in healthy volunteers and patients with AF or heart failure with preserved ejection fraction (HFpEF). HRV is a marker of vagus nerve activity and can be easily measured by software calculating the distance between consecutive R waves on the ECG. BSEVP are a surrogate for the central projections of the vagus nerve. Patients will be randomized into 4 groups in a 2x2 factorial design. LLTS will be delivered through a transcutaneous electrical nerve stimulation (TENS) device for 15 minutes. HRVdb, HRV and BSEVP will be measured before and after LLTS and compared.
- Conditions
- Atrial Fibrillation, Heart Failure, Diastolic
- Being tested
- Parasym
- Medical subject headings
- Atrial Fibrillation, Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParasymDevice
Tragus stimulation
| Study group | Role | What they receive |
|---|---|---|
| Frequency 20Hz; amplitude 1mA below discomfort threshold | Experimental | Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 20Hz; amplitude 1mA below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. Receives: Device: Parasym |
| Frequency 5Hz; amplitude 1mA below discomfort threshold | Active comparator | Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 5Hz; amplitude 1mA below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. Receives: Device: Parasym |
| Frequency 20Hz; amplitude 50% below discomfort threshold | Active comparator | Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 20Hz; amplitude 50% below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. Receives: Device: Parasym |
| Frequency 5Hz; amplitude 50% below discomfort threshold | Active comparator | Patients will receive tragus stimulation for 15 minutes using the following settings: Frequency 5Hz; amplitude 50% below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. Receives: Device: Parasym |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate variability
Heart rate variability is a marker of vagus nerve activity and can be easily measured by PC-based ECG software calculating the distance between consecutive R waves on the ECG. Both time domain [standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences of the normal-to-normal intervals (RMSSD)] and frequency domain [low frequency (LF; 0.04-0.15 Hz), high frequency (HF; 0.15-0.4 Hz), and LF/HF ratio] measures will be analyzed.
Measured: 15 minutes
Mental arithmetic stress test
Mental arithmetic stress test is a measure of sympathetic activity and will be performed by asking the patient to consistently subtract 7 from 500 for a period of 2 minutes. Blood pressure will be measured before and after the test, before and during stimulation and the maximum blood pressure during the test will be the outcome of interest.
Measured: 15 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study start30 Nov 2021
- Primary completionOct 2024 (estimated)
- Study completionFeb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stavros Stavrakis, MD, PhD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04682704
- Sponsor's protocol ID
- 12708
- Acronym
- LLT-SPANS
- Status last verified
- Feb 2024
- First submitted
- 8 Dec 2020
- Last updated
- 21 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Different Low-Level Tragus Stimulation Parameters On Autonomic Nervous System Function
- ClinicalTrials.gov ID
- NCT04682704
- Acronym / sponsor ID
- LLT-SPANS / 12708
- Conditions
- Atrial Fibrillation, Heart Failure, Diastolic
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Feb 2025 (estimated)
- First posted
- 24 Dec 2020 (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.
Low level transcutaneous vagus nerve stimulation (LLTS) involves delivery of electrical impulses transcutaneously at the auricular branch of vagus nerve and it has been shown to have anti-inflammatory and anti-arrhythmic effects. In previous studies from our laboratory, we found that LLTS significantly suppressed atrial fibrillation (AF) inducibility and decreased AF duration. The anti-arrhythmic effects of LLTS were similar to those delivered to the cervical VN trunk. LLTS for just one hour significantly shortened the AF duration and decreased inflammatory cytokines. We have also shown that LLTS leads to favorable heart rate variability (HRV) changes and cardiac mechanics in patients with diastolic dysfunction. These results support the use of LLTS as a novel non-pharmacological, non-ablative treatment modality for AF and possibly other inflammatory conditions. However, the optimal stimulation parameters of LLTS remain to be determined.
In this study, we aim to examine the effect of 2 different frequencies (5Hz and 20Hz) and 2 different amplitudes (50% below the pain threshold and 1mA below the pain threshold) of LLTS on heart rate variability with deep breathing (HRVdb), mental arithmetic stress test (MAST), frequency domain measures of heart rate variability (HRV) and brain stem evoked potentials (BSEVP) in healthy volunteers and patients with AF or heart failure with preserved ejection fraction (HFpEF). HRV is a marker of vagus nerve activity and can be easily measured by software calculating the distance between consecutive R waves on the ECG. BSEVP are a surrogate for the central projections of the vagus nerve. Patients will be randomized into 4 groups in a 2x2 factorial design. LLTS will be delivered through a transcutaneous electrical nerve stimulation (TENS) device for 15 minutes. HRVdb, HRV and BSEVP will be measured before and after LLTS and compared.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Frequency 20Hz; amplitude 1mA below discomfort threshold | Experimental | Device: ParasymPatients will receive tragus stimulation for 15 minutes using the following settings: Frequency 20Hz; amplitude 1mA below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. |
| Frequency 5Hz; amplitude 1mA below discomfort threshold | Active comparator | Device: ParasymPatients will receive tragus stimulation for 15 minutes using the following settings: Frequency 5Hz; amplitude 1mA below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. |
| Frequency 20Hz; amplitude 50% below discomfort threshold | Active comparator | Device: ParasymPatients will receive tragus stimulation for 15 minutes using the following settings: Frequency 20Hz; amplitude 50% below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. |
| Frequency 5Hz; amplitude 50% below discomfort threshold | Active comparator | Device: ParasymPatients will receive tragus stimulation for 15 minutes using the following settings: Frequency 5Hz; amplitude 50% below discomfort threshold. Continuous ECG will be recorded to assess heart rate variability. |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female patients older than 21 year old
- Healthy volunteers free from diagnosis of AF, heart failure, coronary artery disease or diseases that affect the autonomic nervous system.
- Patients with Paroxysmal Atrial Fibrillation
- Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)
Key exclusion criteria (11 listed)
- Recent (<6 months) stroke
- Recent (<6 months) myocardial infarction
- Heart failure (NYHA class III or IV)
- Left ventricular ejection fraction <50%
- Recurrent vaso-vagal syncopal episodes
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 |
|---|---|---|
| ParasymTragus stimulation | Device | Frequency 20Hz; amplitude 1mA below discomfort threshold, Frequency 20Hz; amplitude 50% below discomfort threshold, Frequency 5Hz; amplitude 1mA below discomfort threshold, Frequency 5Hz; amplitude 50% below discomfort threshold |
Primary outcome
Heart rate variability
Time frame: 15 minutes
Heart rate variability is a marker of vagus nerve activity and can be easily measured by PC-based ECG software calculating the distance between consecutive R waves on the ECG. Both time domain [standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences of the normal-to-normal intervals (RMSSD)] and frequency domain [low frequency (LF; 0.04-0.15 Hz), high frequency (HF; 0.15-0.4 Hz), and LF/HF ratio] measures will be analyzed.
Mental arithmetic stress test
Time frame: 15 minutes
Mental arithmetic stress test is a measure of sympathetic activity and will be performed by asking the patient to consistently subtract 7 from 500 for a period of 2 minutes. Blood pressure will be measured before and after the test, before and during stimulation and the maximum blood pressure during the test will be the outcome of interest.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2024.
- Individual participant dataSharing planned: Undecided
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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.
Stavros Stavrakis, MD, PhD principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Parasym in people with Atrial Fibrillation and Heart Failure, Diastolic, run by University of Oklahoma at 1 site in United States.
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 4 inclusion and 11 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 21 Feb 2024. 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 United States. 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 Karrie Meeks (4052714742, karrie-meeks@ouhsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate variability (time frame: 15 minutes). The study lists 2 primary outcomes in all. 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 21 Feb 2024; AzTrials last refreshed its copy on 31 Oct 2026.