Understanding the Effects of Transauricular Vagus Nerve Stimulationon on Neural Networks and Autonomic Nervous System

Not Applicable

Recruiting

• Conditions: Healthy Volunteers
• Interventions: Device: Transauricular vagus nerve stimulation (taVNS)

• Registration Number: NCT05801809
• Lead Sponsor: Spaulding Rehabilitation Hospital

Brief Summary

This trial aims to perform an exploratory, mechanistic, randomized double-blind sham-control trial in healthy participants to assess the physiologic effects of a single 60 minutes session of bilateral taVNS, on neural networks and autonomic function.

Detailed Description

Several studies have shown promising results of taVNS to treat various disorders such as depression, anxiety, Alzheimer's disease, headache, obesity, and diabetes. However, no mechanistic studies have investigated the taVNS neural network and autonomic nervous system effects of this technique. Therefore, we aim to assess how taVNS can affect EEG metrics and HRV and assess its safety. Also, we aim to evaluate predictors that can influence the response to taVNS, so understanding the variables associated with response to taVNS can help the design of future clinical trials to maximize the effects of this intervention.

Study Timeline

• Study First Submitted: 2023-02-27
• Study First Submitted QC: 2023-03-24
• Study First Posted: 2023-04-06
• Study Start: 2023-04-26
• Primary Completion: 2023-09-23
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-14
• Last Update Posted: 2024-06-18
• Study Completion: 2025-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Able to provide informed consent to participate in the study.
2. Subject is older than 18 years.
3. Subjects should be naive to the stimulation (taVNS)

Exclusion Criteria

1. Pregnancy.

2. Subjects who have had a neuropsychiatric or a cardiac disorder diagnosis and have received treatment and chronic medication in the past six months, or who have functional deficits as a result.

3. History of alcohol or drug abuse within the past 6 months as self-reported.

4. Presence of the following contraindication to transauricular vagus nerve stimulation

   1. Ferromagnetic metal in the head and in the cranium (e.g., plates or pins, bullets, shrapnel)
   2. Implanted cranial electronic medical devices (e.g., cochlear implants)
   3. Implanted cardiac devices (e.g., pacemaker)

5. Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure, or chronic obstructive pulmonary disease).

6. Uncontrolled epilepsy, as defined by previous clinical seizures in the past 3 months in patients with treatment for epilepsy.

7. Suffering from severe depression (as defined by a score of >30 in the Beck Depression Inventory).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham taVNS	Transauricular vagus nerve stimulation (taVNS)	Sham condition will have the same device, with an earset, and conductive eartips placed in the same location of the active stimulation; however during 60 min there will be no current and the device will be turned off.
Active taVNS	Transauricular vagus nerve stimulation (taVNS)	TaVNS will be administered by an earset, with conductive eartips placed on the auricular concha of the ears, connected to a stimulator, and during active stimulation, we stimulate both the cymba conchae and external auditory canal of both left and right ears with the following parameters: 30Hz, 200-250 us, and with adjustable intensity for 60 min.

Primary Outcome Measures

Name	Time	Method
Resting-state electroencephalogram (EEG)	Change from baseline resting-state EEG at 60 minutes.	Electroencephalogram (EEG) will be recorded using the 64-channel EGI system (Electrical Geodesics, Inc)(EGI, Eugene, USA) using a high-density electrode array from two resting state conditions: eyes open and eyes closed. Fourier transformation (STFT) will be applied to filter the data into five typically analyzed frequency bands, delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (30-80 Hz) bands.
Quantitative sensory testing (QST)	Change from baseline QST at 60 minutes.	We will find the pain-60 temperature by applying a thermode on the right forearm and delivering short heats that we increased, 1°C each wave, gradually from 41 to 48°C until patients rated their level of pain as 60, generated by a TSA-II Stimulator (Medoc Ltd). Once determined, we will administer the test stimulus for 30s at that temperature and ask them to rate their levels of pain at 10, 20, and 30s. For the conditioned stimulus, the left hand of the subject will be immersed in water at 10 to 12°C for 30s. Then, the same temperature will be applied to the right forearm - with the left hand still immersed - at 10, 20, and 30s. CPM response will be calculated as the difference between the average pain ratings from the test stimulus minus the conditioned stimulus.
Electroencephalogram (EEG) event-related potentials	Change from baseline EEG event-related potentials at 60 minutes.	Electroencephalogram (EEG) will be recorded using the 64-channel EGI system (Electrical Geodesics, Inc)(EGI, Eugene, USA) using a high-density electrode array continuously during visual task stimulus presentation and go/no-go task. Event-related potential amplitudes and latencies will be measured from frontal, central, parietal, and occipital areas. We will analyze five frequency bands, delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (30-80 Hz) bands.

Secondary Outcome Measures

Name	Time	Method
Heart rate variability (HRV)	Change from baseline HRV at 60 minutes.	HRV will be collected from the non-dominant hand following a standardized protocol. The measurements will be taken at baseline, during, and after stimulation.

Trial Locations

Locations (1)

Spaulding Hospital Cambridge; 🇺🇸 Cambridge, Massachusetts, United States