TENS of Auricular Vagal Nerve for Radiation Necrosis

June 25, 2026 updated by: Virginia Commonwealth University

Transcutaneous Auricular Vagal Nerve Stimulation for Treatment of Radiation Necrosis

This is a multi-center, randomized, blinded trial evaluating the effect of transcutaneous auricular vagal nerve stimulator (taVNS) on radiation necrosis-related cerebral edema. In this study, consenting and eligible patients will be assigned to one of two arms: treatment (Arm 1) or sham (Arm 2). Patients in both arms will have imaging performed and tissue and blood collected for assessment of changes in area of contrast enhancement and cerebral edema, inflammatory markers, and markers of blood-brain barrier permeability.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
        • Contact:
        • Principal Investigator:
          • Ryan Cleary, MD

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • History of glioma or metastatic brain lesion previously treated with whole brain radiation, stereotactic radiation surgery, or fractionated radiation therapy
  • Magnetic resonance imaging (MRI) findings consistent with possible radiation necrosis within 6 weeks prior to enrollment.
  • Candidate for tissue biopsy and Laser Interstitial Thermal Therapy (LITT) ablation of the lesion
  • At least 18 years of age
  • If on corticosteroids, able to discontinue at least 5 days prior to start of transcutaneous auricular vagus nerve stimulation (taVNS) (Arm 1) or sham treatment (Arm 2). A stable physiologic dose of corticosteroids, if used as hormone replacement therapy, may be allowed upon discussion with the investigator. 6. Ability to understand and willingness to sign an institutional review board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

  • New onset neurologic deficits secondary to radiation necrosis requiring initiation of dexamethasone therapy or other intervention prior to enrollment
  • Currently receiving bevacizumab for treatment of radiation necrosis or has received bevacizumab < 6 weeks prior to study enrollment.
  • Currently receiving any investigational agents for treatment of radiation necrosis or has participated in a study of an investigational agent for radiation necrosis within 3 weeks prior to study enrollment.
  • History of cardiac conduction disorders or presence of implanted electronic devices
  • Active Crohn's disease or other inflammatory bowel disease.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

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: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Sham Comparator: Sham
Device: Sham
TENS (transcutaneous electrical nerve stimulation) unit connected to an earpiece that fits into the concha of the ear, with no stimulation twice daily for 12 to 14 days prior to planned LITT ablation.
Experimental: Transcutaneous Auricular Vagal Nerve Stimulation (taVNS)
Device: Transcutaneous auricular vagal nerve stimulation (taVNS)
Transcutaneous auricular vagal nerve stimulation (taVNS) stimulation twice daily for 12 to 14 days prior to planned LITT ablation via TENS (transcutaneous electrical nerve stimulation) unit connected to an earpiece that fits into the concha of the ear.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Assess changes in the serum inflammatory marker Tumor Necrosis Factor (TNF)-alpha
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker TNF-alpha utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assess changes in serum inflammatory marker Interleukin 12 (IL-12)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in (IL-12) serum inflammatory marker utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker granulocyte-macrophage colony-stimulating factor (GMCSF)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker GMCSF utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker Interferon gamma (IFN gamma)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker IFN gamma utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin 1 beta (IL-1b)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker IL-1b utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin-10 (IL-10)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker IL-10 utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin 13 (IL-13)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker IL-13 utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin (IL-2)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker IL-2 utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory markers interleukin 17 (IL-17A)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory markers IL-17A utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin 4 (IL-4)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory marker IL-4 utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin 5 (IL-5)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory markers IL-5 utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin 6 (IL-6)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory markers IL-6 utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in serum inflammatory marker interleukin 8 (IL-8)
Time Frame: Baseline, 1 week, and 2 weeks following intervention
Percent change in serum inflammatory markers IL-8 utilizing serum inflammatory marker analysis from collected blood samples
Baseline, 1 week, and 2 weeks following intervention
Assess changes in biomarker Neurofilament light chain (NFL) of central nervous system (CNS) injury following treatment
Time Frame: Baseline, and 2 weeks following intervention
Percent change of NFL marker of CNS inflammation utilizing serum inflammatory marker analysis from collected blood samples
Baseline, and 2 weeks following intervention
Assess changes in biomarker platelet-derived growth factor receptor-beta (PDGFR-beta) of central nervous system (CNS) injury following treatment
Time Frame: Baseline, and 2 weeks following intervention
Percent change of marker PDGFR-beta of CNS inflammation utilizing serum inflammatory marker analysis from collected blood samples
Baseline, and 2 weeks following intervention
Assess changes in biomarker vascular endothelial growth factor (VEGF) of central nervous system (CNS) injury following treatment
Time Frame: Baseline, and 2 weeks following intervention
Percent change of marker VEGF of CNS inflammation utilizing serum inflammatory marker analysis from collected blood samples
Baseline, and 2 weeks following intervention
Assess changes in biomarkers of blood-brain barrier (BBB) permeability following treatment
Time Frame: Baseline, and 2 weeks following intervention
Percent change of BBB permeability
Baseline, and 2 weeks following intervention
Assess interval changes in radiation necrosis on MRI after treatment w taVNS
Time Frame: Baseline, and 2 weeks following intervention
Percent changes in areas of contrast enhancement and perilesional T2-weighted fluid-attenuated inversion recovery (T2/FLAIR) Hypersensitivity on magnetic resonance imaging (MRI). On these images, areas with higher water content suck as edema, inflammation, or demyelination, appear brighter compared to surrounding tissue.
Baseline, and 2 weeks following intervention
Assess interval changes in cerebral edema on MRI after treatment
Time Frame: Baseline, and 2 weeks following intervention
Percent changes in areas of contrast enhancement and perilesional T2/FLAIR Hypersensitivity on MRI
Baseline, and 2 weeks following intervention

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Virginia Commonwealth University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ryan Cleary, MD, Virginia Commonwealth University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 31, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 25, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 2, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MCC-25-22821

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

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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