Vagus Nerve Stimulation (VNS) Electroencephalogram (EEG) Protocol Supplement

The study will examine the autonomic, physiologic and neurophysiologic effects of implanted Vagus Nerve Stimulation (VNS) in treatment-resistant depression patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Device: Vagus Nerve Stimulation

Detailed Description

The purpose of this study is to examine the autonomic and physiologic effects of implanted VNS in treatment-resistant depression patients. To examine the neurophysiologic effects of Vagus Nerve Stimulation (VNS) in treatment-resistant depression.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Irakli Kaloiani; Phone Number: 650-800-6920; Email: ikalo@stanford.edu
• Study Contact Backup: Name: Katina Marchione; Email: kfmarch@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be at least 18 years old.
2. Participants must be able to read, understand and have the capacity to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.
3. Proficiency in English sufficient to complete questionnaire and follow instructions during fMRI assessments and iTBS interventions.
4. Willingness to comply with all study procedures and the ability to communicate with study personnel about adverse events and other clinically important information

5. Participant must be currently enrolled in the REVEAL study and implanted with a VNS device for the clinical indication of Major Depressive Disorder (MDD)

   a. Clinical Indication of MDD as defined: Participant has a diagnosis of chronic (≥ 2 years) or ≥ 4 recurrent depressive episodes as defined by DSM-5 criteria documented using the MINI criteria and psychiatric medical record review.

6. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
7. Access to ongoing psychiatric care before and after completion of the study.
8. In good general health, as evidenced by medical history
9. Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

1. Participant is pregnant
2. Participant does not speak or read English
3. Any other clinical reasons deemed by the investigator of the study for which the participant would not be an appropriate candidate for the study.
4. Contraindication to MRI (ferromagnetic metal in their body)
5. Contraindication to EEG
6. Medication Contraindications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Participants implanted with VNS; Participants receiving vagus nerve stimulation through an implanted Vagus Nerve Stimulation Device.	Device: Vagus Nerve Stimulation; Participants receiving vagus nerve stimulation through an implanted Vagus Nerve Stimulation Device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gamma and theta band phase-amplitude coupling	Measurement of EEG and ECG to quantify changes in phase-amplitude coupling in the gamma and theta band related to chronic VNS	Baseline, Week 6 and Week 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting state functional connectivity between the left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex	Measurement of changes in resting state functional connectivity between the left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex with chronic VNS using fMRI.	Baseline, Week 6 and Week 19
Heart brain coupling	Measurement of heart brain coupling (heart rate entrainment in response to trains of intermittent theta burst stimulation) with VNS via an EKG sweep	Week 19
Heart rate	Measure heart rate and heart rate variability with VNS	Baseline, Week 6 and Week 19

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Galvanic Skin Response	Measure the changes in sweat gland activity that affects the skin's electrical properties with VNS	Baseline, Week 6 and Week 19
Blood pressure	Measure the changes in blood pressure with VNS	Baseline, Week 6 and Week 19
Respiratory rate	Measure the changes in respiratory rate with chronic VNS.	Baseline, Week 6 and Week 19
Pupil diameter	Measure the changes in pupil diameter with chronic VNS using pupillometry.	Baseline, Week 6 and Week 19

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Study Director: Christopher Austelle, MD, Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 19, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Therapeutics; Electric Stimulation Therapy; Vagus Nerve Stimulation
• Other Study ID Numbers: 80038

Drug and device information, study documents

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