Synaptic Plasticity in the Epicardial Ganglionated Plexi

NCT ID: NCT05034419

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-24
• Study Completion Date: 2024-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Active stimulation

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.

Group Type: EXPERIMENTAL

Parasym

Intervention Type: 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.

Sham stimulation

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.

Group Type: SHAM_COMPARATOR

Sham stimulation

Intervention Type: DEVICE

Sham stimulation

Interventions

Parasym

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.

Intervention Type: DEVICE

Sham stimulation

Sham stimulation

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Male and female patients older than 21 year old

2. Patient is going to have open heart surgery.

Exclusion Criteria

1. Patients undergoing emergent open heart surgery.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oklahoma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

OU Medical Center

Oklahoma City, Oklahoma, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Stavros Stavrakis

Role: CONTACT

stavros-stavrakis@ouhsc.edu

4052714742

Facility Contacts

Stavros Stavrakis, MD

Role: primary

Stavros-Stavrakis@ouhsc.edu

405-313-2197

Other Identifiers

11474

Identifier Type: -

Identifier Source: org_study_id