Cerebral Edema, Radiation Necrosis
Conditions
Keywords
Radiation Necrosis
Brief summary
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.
Interventions
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.
DEVICESham
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.
Sponsors
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess changes in the serum inflammatory marker Tumor Necrosis Factor (TNF)-alpha | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess changes in serum inflammatory marker Interleukin 12 (IL-12) | 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 |
| Assess changes in serum inflammatory marker granulocyte-macrophage colony-stimulating factor (GMCSF) | Baseline, 1 week, and 2 weeks following intervention | Percent change in serum inflammatory marker GMCSF utilizing serum inflammatory marker analysis from collected blood samples |
| Assess changes in serum inflammatory marker Interferon gamma (IFN gamma) | 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 |
| Assess changes in serum inflammatory marker interleukin 1 beta (IL-1b) | 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 |
| Assess changes in serum inflammatory marker interleukin-10 (IL-10) | 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 |
| Assess changes in serum inflammatory marker interleukin 13 (IL-13) | 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 |
| Assess changes in serum inflammatory marker interleukin (IL-2) | 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 |
| Assess changes in serum inflammatory markers interleukin 17 (IL-17A) | 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 |
| Assess changes in serum inflammatory marker interleukin 4 (IL-4) | 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 |
| Assess changes in serum inflammatory marker interleukin 5 (IL-5) | 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 |
| Assess changes in serum inflammatory marker interleukin 6 (IL-6) | 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 |
| Assess changes in serum inflammatory marker interleukin 8 (IL-8) | 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 |
| Assess changes in biomarker Neurofilament light chain (NFL) of central nervous system (CNS) injury following treatment | Baseline, and 2 weeks following intervention | Percent change of NFL marker of CNS inflammation utilizing serum inflammatory marker analysis from collected blood samples |
| Assess changes in biomarker platelet-derived growth factor receptor-beta (PDGFR-beta) of central nervous system (CNS) injury following treatment | Baseline, and 2 weeks following intervention | Percent change of marker PDGFR-beta of CNS inflammation utilizing serum inflammatory marker analysis from collected blood samples |
| Assess changes in biomarker vascular endothelial growth factor (VEGF) of central nervous system (CNS) injury following treatment | Baseline, and 2 weeks following intervention | Percent change of marker VEGF of CNS inflammation utilizing serum inflammatory marker analysis from collected blood samples |
| Assess changes in biomarkers of blood-brain barrier (BBB) permeability following treatment | Baseline, and 2 weeks following intervention | Percent change of BBB permeability |
| Assess interval changes in radiation necrosis on MRI after treatment w taVNS | 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. |
| Assess interval changes in cerebral edema on MRI after treatment | Baseline, and 2 weeks following intervention | Percent changes in areas of contrast enhancement and perilesional T2/FLAIR Hypersensitivity on MRI |
Countries
United States
Contacts
CONTACTAmy Erickson
PRINCIPAL_INVESTIGATORRyan Cleary, MD
Virginia Commonwealth University
Outcome results
None listed