Synaptic Plasticity in the Epicardial Ganglionated Plexi

NCT05034419 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 11474
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (3)

• choline acetyltransferase

  Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for choline acetyl transferase (ChAT) will be performed

  30 minutes

• tyrosine hydroxylase

  Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for tyrosine hydroxylase will be performed

  30 minutes

• synaptophysin

  Biopsy from ganglionated plexus (GP) tissue will be taken and histological staining for synaptophysin will be performed

  30 minutes

Study Arms (2)

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.

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.

Device: Sham stimulation

Interventions

Parasym DEVICE

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.

Active stimulation

Sham stimulation DEVICE

Sham stimulation

Sham stimulation

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients older than 21 year old
• Patient is going to have open heart surgery.

You may not qualify if:

• \. Patients undergoing emergent open heart surgery.

Sponsors & Collaborators

• University of Oklahoma: lead

Study Sites (1)

OU Medical Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Stavros Stavrakis

CONTACT

4052714742; stavros-stavrakis@ouhsc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 5, 2021
• Study Start: March 24, 2021
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 6, 2024

Record last verified: 2024-03

Locations

US (1)