ABVN Phase 2-Studying the Effect of Stimulation on the Auricular Branch of the Vagal Nerve (ABVN2)

Effect of Electrical Stimulation of the Auricular Branch of the Vagus Nerve (ABVN) on Cervical Vagus Nerve Action Potentials Phase 2

The purpose of this study is to find out if we can gain access to the vagus nerve which is largely an internal nerve that controls stomach function. We hope to gain access to the internal vagus nerve by electrically stimulating the nerve around the external ear. If we can do this then we hope that this will help our treatment of patients with nausea and vomiting and disordered stomach function

Study Overview

• Status: Active, not recruiting
• Conditions: Gastroparesis
• Intervention / Treatment: Device: ML1101 Stimulus Isolator; Procedure: Vagal Maneuver

Detailed Description

Subjects will undergo transcutaneous stimulation of the auricular branch of the vagus nerve and also undergo blood draw before, after stimulation and later a third draw after a period of no stimulation. Healthy subjects will also undergo vagal maneuver using the Multi Array Electrodes (MEA). Gastroparetic subjects will also undergo vagal maneuver using either the regular EKG electrodes or the MEA electrodes.

Subjects will also complete health history questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria healthy volunteers

• Healthy volunteers with no gastric symptoms or conditions (except due to COVID 19)
• Aged 18-80 years
• Willing to have electrodes placed in the external ear (ABVN arm)
• Willing to perform vagal activity maneuver (Vagal arm)
• Willing to have 1 tablespoon (15 ml) of blood drawn at 3 time points

Inclusion Criteria gastroparesis subjects

• Gastroparesis subjects with a confirmed diagnosis of gastroparesis from a GI physician
• Have a formal diagnosis of gastroparesis or are seeing the GI physician for symptoms related to gastroparesis
• Aged 18-80 years
• Willing to have electrodes placed in the external ear (ABVN arm)
• Willing to perform vagal activity maneuver (Vagal arm)
• Willing to have 1 tablespoon (15 ml) of blood drawn at 3 time points

Exclusion Criteria:

• Unable to provide consent
• Pregnant females
• Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Subjects; Subjects who have no gastric symptoms or conditions	Device: ML1101 Stimulus Isolator; Electrical stimulation electrodes will be placed on the ear with the intensity of the current being increased by 10 percent every 60 seconds, the subject will grade the intensity of the current on a scale of 0-10. Increasing of the current will occur until the subject reports a comfortable level. Once the target level has been achieved the stimulation will be delivered for 2 minutes.; Procedure: Vagal Maneuver; Subjects will undergo the following procedures to stimulate the vagus nerve.; Cough: 6 to 8 forceful coughs; Cold stimulus: a washcloth soaked in ice water will be placed on the face for 10 seconds.; Carotid massage; Gagging: a tongue depressor will be inserted for 10 seconds into the mouth touching the back of the mouth.; Valsalva maneuver: subjects will will be asked to bear down as if they were having a bowel movement. They will be asked to blow through a mouthpiece that is hooked to a machine that measures how hard they are blowing.; Eating: Subjects will be asked to drink water ( 8oz or 1 cup) or/ and Ensure Original ( 8 oz or 1 cup) that has 220 calories after fasting overnight to see that effect on vagal activity during eating.
Experimental: Gastroparesis Subjects; Subjects with a confirmed diagnosis of gastroparesis.	Device: ML1101 Stimulus Isolator; Electrical stimulation electrodes will be placed on the ear with the intensity of the current being increased by 10 percent every 60 seconds, the subject will grade the intensity of the current on a scale of 0-10. Increasing of the current will occur until the subject reports a comfortable level. Once the target level has been achieved the stimulation will be delivered for 2 minutes.; Procedure: Vagal Maneuver; Subjects will undergo the following procedures to stimulate the vagus nerve.; Cough: 6 to 8 forceful coughs; Cold stimulus: a washcloth soaked in ice water will be placed on the face for 10 seconds.; Carotid massage; Gagging: a tongue depressor will be inserted for 10 seconds into the mouth touching the back of the mouth.; Valsalva maneuver: subjects will will be asked to bear down as if they were having a bowel movement. They will be asked to blow through a mouthpiece that is hooked to a machine that measures how hard they are blowing.; Eating: Subjects will be asked to drink water ( 8oz or 1 cup) or/ and Ensure Original ( 8 oz or 1 cup) that has 220 calories after fasting overnight to see that effect on vagal activity during eating.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amplitude of vagal nerve compound action	To measure the amplitude of vagal nerve compound action potentials during stimulation of the auricular branch of the vagal nerve and during vagal maneuvers.	3 hours
Respiratory Changes in heart rate during stimulation	To measure respiratory changes in heart rate during stimulation of the auricular branch of the vagal nerve and also during the vagal maneuvers phase.	3 hours
Changes in amplitude of the surface electrogastrogram	To measure the changes of surface electrogastogram during stimulation of the auricular branch of the vagal nerve and also during the vagal maneuvers phase.	3 hours.
Changes in gastric hormones	To measure the effect of stimulation of the auricular branch of the vagal nerve and/or of vagal maneuvers on gastric hormones.	3 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure respiratory changes in heart rate during ABVN and also during the vagal maneuvers phase.	To measure respiratory changes in heart rate during ABVN and during the vagal maneuvers using skin electrodes over right and left vagus nerve, via EKG during ABVN stimulation and also during the vagal maneuvers phase.	Two Years
measure changes in the amplitude of the surface electrogastrogram during ABVN	To measure changes in the amplitude of the surface electrogastrogram with skin electrodes over right and left vagus nerve during ABVN and also during the vagal maneuvers phase.	Two Years
To measure the Heart rate variability (HRV), vagal nerve compound action potentials and in subjects undergoing VNS Therapy	Using skin electrodes for an EKG over right and left vagus nerve during ABVN stimulation and also during the vagal maneuvers phase in patients being treated for Focal/partial seizures.	Two Years
To measure the effect of ABVN stimulation on the gastric hormones in healthy and gastroparetic subjects.	In gastroparetic subjects and healthy volunteers; blood draws will be done at a baseline time point, after stimulation to the ABVN in healthy patients and after turning the gastric stimulator off in patients with gastroparesis, and then after a recovery period for both groups. The blood will then be processed into serum and that serum will then be tested by an Indiana University Lab to determine changes in Insulin, Glucose and C-peptide levels after each phase.	Two Years
measure the amplitude of vagal nerve compound action potentials in healthy volunteers undergoing PENFS	To measure the amplitude of vagal nerve compound action potentials in healthy volunteers undergoing PENFS	Two years
measure the parasympathetic and sympathetic vagal nerve activity in healthy volunteers undergoing PENFS	To measure the parasympathetic and sympathetic vagal nerve activity in healthy volunteers undergoing PENFS	Two Years
measure the changes in the amplitude of the surface electrogastrogram (EGG)	o measure the changes in the amplitude of the surface electrogastrogram (EGG) in healthy volunteers after PENFS	Two Years
ssess if the wearable device can predict/detect the onset of symptoms reported by study participants wearing the wrist watch	The investigators will use the Corsano watch/bracelet To assess if the wearable device can predict/detect the onset of symptoms reported by study participants wearing the wrist watch. The Coordinators will have access to Corsano's data base function to monitor information and usage of the Corsano bracelet	Two Years
To assess participant autonomic responses to taVNS stimulation.	In order to assess participant autonomic responses to taVNS stimulation, skin electrodes will be placed over the right and left vagus nerve during ABVN stimulation and also during the vagal maneuvers phase. This will give an EKG type of readout which will be used to determine changes in biometric functions during the assessment.	Two Years
measure the amplitude of vagal nerve compound action potentials in gastroparetic subjects	To measure the amplitude of vagal nerve compound action potentials in gastroparetic subjects with symptoms of nausea and vomiting with skin electrodes over right and left vagus nerve during ABVN stimulation and also during the vagal maneuvers phase	Two Years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The investigators would like to study the autonomic responses for EDS patients and matched controls using wearable watch device and transcutaneous stimulation of the auricular branch of the vagal nerve stimulation (TaVNS)	Investigators will be studying the autonomic responses for EDS patients and matched controls using wearable watch device after transcutaneous stimulation of the auricular branch of the vagal nerve stimulation (TaVNS). This device will be used to gather daily information from various autonomic and sympathetic biometric functions over the course of one month. The readings will then be assessed by Purdue University biostatisticians to detect patterns and variants in the different functions.	Two Years

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Thomas V Nowak, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Gastroparesis
• Other Study ID Numbers: 2006075899- A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data may be shared with other researchers for similar purposes as to this study
• IPD Sharing Time Frame: Three years after study completion
• IPD Sharing Access Criteria: None as of yet.
• IPD Sharing Supporting Information Type: ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes