TENS of Auricular Vagal Nerve for Radiation Necrosis

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: Not yet recruiting
• Conditions: Cerebral Edema; Radiation Necrosis
• Intervention / Treatment: Device: Transcutaneous auricular vagal nerve stimulation (taVNS); Device: Sham

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amy Erickson; Phone Number: 804-828-9165; Email: amy.erickson@vcuhealth.org

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
      • Contact: Amy Erickson; Phone Number: 804-828-9165; Email: amy.erickson@vcuhealth.org
      • Principal Investigator: Ryan Cleary, MD

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Assess changes in the serum inflammatory marker Tumor Necrosis Factor (TNF)-alpha	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

Outcome Measure	Measure Description	Time Frame
Assess changes in serum inflammatory marker Interleukin 12 (IL-12)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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	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	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	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	Percent change of BBB permeability	Baseline, and 2 weeks following intervention
Assess interval changes in radiation necrosis on MRI after treatment w taVNS	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	Percent changes in areas of contrast enhancement and perilesional T2/FLAIR Hypersensitivity on MRI	Baseline, and 2 weeks following intervention

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Ryan Cleary, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Radiation Necrosis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Edema
• Other Study ID 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