Atrial FibrillationPhase 1SNAP-GPNCT05034419
Synaptic Plasticity in the Epicardial Ganglionated Plexi
A Phase 1 study testing Parasym in people with Atrial Fibrillation, run by University of Oklahoma at 1 site in United States.
Trial summary
Atrial fibrillation (AF) is the most common arrhythmia and the prevalence increase with age. Autonomic nervous system play a critical role in the initiation and maintenance of AF. Read more about this study
- Who is it for?
- Ages 21 to 90 years
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Parasym
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2021to Dec 2024
- Phase
- Phase 1
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients older than 21 year old
- Patient is going to have open heart surgery.
Who cannot join
- 1. Patients undergoing emergent open heart surgery.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
OU Medical Center
Oklahoma City, Oklahoma, 73104
Stavros Stavrakis, MD, 405-313-2197, Stavros-Stavrakis@ouhsc.edu
About this study
Atrial fibrillation (AF) is the most common arrhythmia and the prevalence increase with age. Autonomic nervous system play a critical role in the initiation and maintenance of AF. The intrinsic cardiac autonomic nervous system includes ganglionated plexus (GP) modulate the level of parasympathetic activity to the heart. Experimental and clinical studies suggest that GP activation plays a significant role in clinical AF in both the initiation of and the maintenance of AF.
Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the GP neurons innervating the heart. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by GP neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation.
Read more
Low level tragus stimulation (LLTS) has been shown to decrease AF burden among patients with paroxysmal AF. However, the exact mechanism remains unclear. The objective of this study is to examine changes in synaptic density of GP neurons in patients with paroxysmal AF and persistent AF compared to those without AF undergoing cardiac surgery. In addition, we aim to examine the effect of LLTS on the synaptic plasticity of the GP neurons. A group of patients undergoing open heart surgery will be randomized to active LLTS for 30 min (pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz) or no stimulation. Biopsy from GP tissue will be taken immediately after stimulation and histological staining for choline acetyl transferase (ChAT), tyrosine hydroxylase (TH) and synaptophysin will be performed to examine synaptic plasticity.
Understanding the effect of LLTS on GP SP will help to determine whether changes in synaptic plasticity can increase or decrease autonomic tone of the heart, and its role in generating the aberrant electrical impulses in the GP around the pulmonary veins that can trigger and drive AF.
- Conditions
- Atrial Fibrillation
- Being tested
- Parasym, Sham stimulation
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParasymDevice
Stimulation will be done under anesthesia for 30 minutes. Stimulation parameters include a pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz. The Parasym devise (Parasym Health, London, UK) will be used for stimulation. The device will be connected to a clip electrode that will be attached to the external ear. In the active group, the ear clip electrode will be attached to tragus in the active stimulation group. This device has been deemed non-significant risk by the FDA. In the control group, no stimulation will be done.
Sham stimulationDevice
Sham stimulation
| Study group | Role | What they receive |
|---|---|---|
| Active stimulation | Experimental | Patients undergoing cardiac surgery will be randomized to active low level tragus stimulation for 30 min (pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz). Stimulation will be provided using the Parasym device. Receives: Device: Parasym |
| Sham stimulation | Sham comparator | Patients undergoing cardiac surgery will be randomized to sham stimulation for 30 min. The Parasym device will be placed on the patient's tragus, but no current will be delivered. Receives: Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
choline acetyltransferase
Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for choline acetyl transferase (ChAT) will be performed
Measured: 30 minutes
tyrosine hydroxylase
Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for tyrosine hydroxylase will be performed
Measured: 30 minutes
synaptophysin
Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for synaptophysin will be performed
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start24 Mar 2021
- Primary completionOct 2024 (estimated)
- Study completionDec 2024 (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.
- More trials run by University of OklahomaThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05034419
- Sponsor's protocol ID
- 11474
- Acronym
- SNAP-GP
- Status last verified
- Mar 2024
- First submitted
- 27 Aug 2021
- Last updated
- 6 Mar 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 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synaptic Plasticity in the Epicardial Ganglionated Plexi
- ClinicalTrials.gov ID
- NCT05034419
- Acronym / sponsor ID
- SNAP-GP / 11474
- Conditions
- Atrial Fibrillation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- 24 Mar 2021 (actual)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 5 Sep 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.
Atrial fibrillation (AF) is the most common arrhythmia and the prevalence increase with age. Autonomic nervous system play a critical role in the initiation and maintenance of AF. The intrinsic cardiac autonomic nervous system includes ganglionated plexus (GP) modulate the level of parasympathetic activity to the heart. Experimental and clinical studies suggest that GP activation plays a significant role in clinical AF in both the initiation of and the maintenance of AF.
Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the GP neurons innervating the heart. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by GP neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation.
Low level tragus stimulation (LLTS) has been shown to decrease AF burden among patients with paroxysmal AF. However, the exact mechanism remains unclear. The objective of this study is to examine changes in synaptic density of GP neurons in patients with paroxysmal AF and persistent AF compared to those without AF undergoing cardiac surgery. In addition, we aim to examine the effect of LLTS on the synaptic plasticity of the GP neurons. A group of patients undergoing open heart surgery will be randomized to active LLTS for 30 min (pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz) or no stimulation. Biopsy from GP tissue will be taken immediately after stimulation and histological staining for choline acetyl transferase (ChAT), tyrosine hydroxylase (TH) and synaptophysin will be performed to examine synaptic plasticity.
Understanding the effect of LLTS on GP SP will help to determine whether changes in synaptic plasticity can increase or decrease autonomic tone of the heart, and its role in generating the aberrant electrical impulses in the GP around the pulmonary veins that can trigger and drive AF.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active stimulation | Experimental | Device: ParasymPatients undergoing cardiac surgery will be randomized to active low level tragus stimulation for 30 min (pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz). Stimulation will be provided using the Parasym device. |
| Sham stimulation | Sham comparator | Device: Sham stimulationPatients undergoing cardiac surgery will be randomized to sham stimulation for 30 min. The Parasym device will be placed on the patient's tragus, but no current will be delivered. |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male and female patients older than 21 year old
- Patient is going to have open heart surgery.
Key exclusion criteria (1 listed)
- 1. Patients undergoing emergent open heart surgery.
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 |
|---|---|---|
| ParasymStimulation will be done under anesthesia for 30 minutes. Stimulation parameters include a pulse width of 200 μs, amplitude of 20 mA and a pulse frequency of 20 Hz. The Parasym devise (Parasym Health, London, UK) will be used for stimulation. The device will be connected to a clip electrode that will be attached to the external ear. In the active group, the ear clip electrode will be attached to tragus in the active stimulation group. This device has been deemed non-significant risk by the FDA. In the control group, no stimulation will be done. | Device | Active stimulation |
| Sham stimulationSham stimulation | Device | Sham stimulation |
Primary outcome
choline acetyltransferase
Time frame: 30 minutes
Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for choline acetyl transferase (ChAT) will be performed
tyrosine hydroxylase
Time frame: 30 minutes
Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for tyrosine hydroxylase will be performed
synaptophysin
Time frame: 30 minutes
Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for synaptophysin will be performed
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Individual participant dataSharing planned: Undecided
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ATRIAL APPENDAGE CLOSURE for ATRIAL FIBRILLATION, Atrial Fibrillation (AF)
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Parasym in people with Atrial Fibrillation, 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 2 inclusion and 1 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 6 Mar 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Stavros Stavrakis (4052714742, stavros-stavrakis@ouhsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
choline acetyltransferase (time frame: 30 minutes). The study lists 3 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 6 Mar 2024.