Auricular Vagal Neuromodulation for Depression and Anxiety in Substance Use Disorder

September 10, 2026 updated by: Daisy Thompson-Lake

Auricular Vagal Neuromodulation Therapy (AVNT™) for the Alleviation of Depression and Anxiety in Substance Use Disorder

This pilot study will evaluate whether home-based auricular vagal neuromodulation therapy (AVNT) is practical, acceptable, and well tolerated for adults receiving treatment for substance use disorder. Participants will use a handheld device that delivers mild electrical stimulation to the ear for approximately 60 minutes each day over 30 days. Researchers will examine whether participants can successfully use the device as directed and complete study procedures. The study will also explore whether use of the device is associated with changes in depression, anxiety, sleep problems, and substance craving.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able and willing to provide informed consent.
  • 18 to 60 years of age.
  • History of substance use disorder involving illicit substances, such as opioids, stimulants, or sedatives.
  • Currently enrolled in treatment for substance use disorder or actively seeking treatment.
  • Score of 11 or greater on the Patient Health Questionnaire-9 (PHQ-9), indicating at least moderate depression symptoms.
  • If taking medication for depression, anxiety, or sleep, on a stable dose for at least 2 weeks before the baseline visit, when feasible.
  • Able to read, speak, and understand English well enough to complete study procedures and questionnaires.16 17• Willing and able to comply with study visits and study procedures for approximately 30 days.

Exclusion Criteria:

  • Currently participating in another research study that includes an active treatment or intervention.
  • Diagnosis of a neurological disorder, such as Parkinson's disease.
  • Permanent implanted metal or electronic device near the ear, including certain hearing, heart, or nerve stimulation devices.
  • Previous surgery involving the vagus nerve.
  • Resting heart rate less than 50 beats per minute.
  • Severe coronary artery disease or heart attack within the past 5 years.
  • Active infection, skin condition, or skin breakdown on or near the outer ear where the device would be placed.
  • History of trigeminal neuralgia within the past year.
  • Pregnant, planning to become pregnant during the study, or suspected to be pregnant.
  • Current severe or unstable psychiatric condition that would interfere with participation, such as active psychosis or acute suicidal risk.
  • Acute intoxication or severe withdrawal symptoms at screening or baseline that would interfere with study participation.
  • Significant abnormalities of the outer ear that would interfere with placement or use of the study device.
  • Current use of another neuromodulation therapy, such as transcranial magnetic stimulation (TMS) or vagus nerve stimulation.
  • Court-mandated addiction treatment.
  • Incarcerated individuals.
  • Unable to provide informed consent or comply with study procedures.
  • Any medical, psychiatric, or social condition that, in the opinion of the investigator, would make participation unsafe or interfere with study results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AVNT Intervention
Participants receive auricular vagal neuromodulation therapy (AVNT) using the Parasym device. At the baseline visit, participants are trained on device use, electrode placement, and stimulation adjustment. Participants then self-administer AVNT at home for approximately 60 minutes daily over a 30-day study period. Stimulation is delivered to the auricular branch of the vagus nerve through an ear electrode placed on the tragus and is adjusted to a comfortable, perceptible level.
Device: Transcutaneous Auricular Vagus Nerve Stimulation
Non-invasive transcutaneous auricular vagus nerve stimulation delivered using the Parasym device. Electrical stimulation is applied to the auricular branch of the vagus nerve through an ear electrode placed on the tragus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment Rate
Time Frame: From enrollment to the end of treatment at 30 days
Number of participants enrolled divided by the number of participants screened for eligibility.
From enrollment to the end of treatment at 30 days
Retention Rate
Time Frame: From enrollment to the end of treatment at 30 days
Percentage of enrolled participants who remain active in the study through the Day 30 follow-up assessment.
From enrollment to the end of treatment at 30 days
Study Completion Rate
Time Frame: From enrollment to the end of treatment at 30 days
Percentage of enrolled participants who complete all required end-of-study assessments at Day 30.
From enrollment to the end of treatment at 30 days
Adherence to AVNT Device Use
Time Frame: From enrollment to the end of treatment at 30 days
Percentage of prescribed AVNT sessions completed during the 30-day study period, based on participant-reported device use and/or device usage records.
From enrollment to the end of treatment at 30 days
Participant-Reported Tolerability of AVNT Using the AVNT Tolerability Assessment
Time Frame: From enrollment to the end of treatment at 30 days
Tolerability will be assessed using the study-specific AVNT Tolerability Assessment. Participants rate the severity of device-related symptoms (ear discomfort/pain, skin irritation, unpleasant stimulation sensations, headache, dizziness/lightheadedness, fatigue, nausea, and other symptoms) as None, Mild, Moderate, or Severe. The assessment also records whether device use resulted in reduced stimulation intensity, paused sessions, early session termination, skipped sessions, contact with the study team, or seeking medical care. Participants additionally provide an overall tolerability rating on a 5-point scale ranging from "Very easy to tolerate" to "Very difficult to tolerate.
From enrollment to the end of treatment at 30 days
Device Return Rate
Time Frame: From enrollment to the end of treatment at 30 days
Percentage of participants who return study-issued AVNT devices at the end-of-study visit or upon withdrawal from the study.
From enrollment to the end of treatment at 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Patient Health Questionnaire-9 (PHQ-9) Score
Time Frame: From enrollment to the end of the study period at 30 days
Change in depression symptom severity as measured by the Patient Health Questionnaire-9 (PHQ-9). Total scores range from 0 to 27, with higher scores indicating more severe depressive symptoms.
From enrollment to the end of the study period at 30 days
Change in Generalized Anxiety Disorder-7 (GAD-7) Score
Time Frame: From enrollment to the end of the study period at 30 days
Change in anxiety symptom severity as measured by the Generalized Anxiety Disorder-7 (GAD-7). Total scores range from 0 to 21, with higher scores indicating more severe anxiety symptoms.
From enrollment to the end of the study period at 30 days
Change in Pittsburgh Sleep Quality Index (PSQI) Score
Time Frame: From enrollment to the end of the study period at 30 days
Change in sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). Total scores range from 0 to 21, with higher scores indicating poorer sleep quality.
From enrollment to the end of the study period at 30 days
Change in Substance Use as Measured by the Timeline Follow-Back (TLFB)
Time Frame: From enrollment to the end of the study period at 30 days
Change in self-reported substance use as measured by the Timeline Follow-Back (TLFB). The TLFB estimates the frequency and quantity of substance use over a specified period, with higher values indicating greater substance use.
From enrollment to the end of the study period at 30 days
Change in Distress Tolerance Scale (DTS) Score
Time Frame: From enrollment to the end of the study period at 30 days
Change in distress tolerance as measured by the Distress Tolerance Scale (DTS). Total scores range from 15 to 75, with higher scores indicating greater ability to tolerate emotional distress.
From enrollment to the end of the study period at 30 days
Change in Neuro-QoL Domain Scores
Time Frame: From enrollment to the end of the study period at 30 days
Change in quality of life as measured by Neuro-QoL domain T-scores. Neuro-QoL scores are standardized to a reference population with a mean of 50 and a standard deviation of 10. Higher scores indicate more of the domain being measured. For anxiety, depression, stigma, and sleep disturbance domains, higher scores indicate worse symptoms.
From enrollment to the end of the study period at 30 days
Change in Craving Ratings During the Cue Reactivity Craving Task
Time Frame: From enrollment to the end of the study period at 30 days
Change in participant-reported craving in response to substance-related cues. Craving ratings range from 0 (no craving) to 100 (strongest craving possible), with higher scores indicating greater craving.
From enrollment to the end of the study period at 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daisy Thompson-Lake

Collaborators

Parasym Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2029

Study Registration Dates

First Submitted

July 15, 2026

First Submitted That Met QC Criteria

September 10, 2026

First Posted (Actual)

September 11, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 10, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 303501

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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