Effects of VNS on RT-induced Inflammation and Prognosis of Patients With NSCLC

Study Overview
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Brief Summary
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Lung cancer (LC) remains a leading cause of death among cancers worldwide. Though radiotherapy is one of the most frequently used treatments, it increases side-effects (pain, fatigue) and inflammation, possibly leading to further tumorigenesis of surviving cancer cells. The purpose of this study is to test the effects of transcutaneous auricular VNS vagal nerve stimulation (taVNS), known to reduce inflammation, on radiotherapy-induced inflammation and other side-effects in LC patients undergoing radiotherapy. In this feasibility study 12 patients with NSCLC stage III (A/B) receiving radiotherapy will be enrolled. Our primary endpoint is the effect of vagus nerve stimulation (VNS) on inflammatory levels (such as CRP and cytokines), immunological factors (neutrophils, monocytes, lymphocytes) and the tumor marker CEA. Our secondary endpoint is the psychological well-being and quality of life of the patients during their radiotherapy treatment.

Official Title
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Effects of Transcutaneous Auricular Vagal Nerve Stimulation on Radiotherapy-induced Inflammation and Prognosis of Patients With Lung Cancer

Conditions
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Lung Cancer, Non-small Cell

Intervention / Treatment
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* Device: Transcutaneous vagus nerve stimulation
* Device: Sham
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >18 years old Patients with non-small cell lung cancer stage III (A or B) Patients receiving radiotherapy or chemoradiotherapy Patients with an HRV < 70 msec Exclusion Criteria: Patients with an active implantable medical device, such as a pacemaker, hearing aid implant or any other implanted electronic device Patients with an implanted or wearable defibrillator. Patients with myocardial disease Patients with arrhythmias Patients with an implanted metallic or electronic device in their head. Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: taVNS<br>Treatment will be carried out twice a day (once before the RT session and 8h later) during 7 weeks. Each treatment takes 30 minutes. | Device: Transcutaneous vagus nerve stimulation<br>* The transcutaneous auricular vagus nerve stimulator Parasym consists of a stimulation unit and a dedicated ear electrode. The stimulation unit, having approximately the size of a common mobile phone, sends out the electrical impulses. It is connected with the ear electrode, which patients wear like an earphone. The patient can regulate and adapt the intensity of the stimulation (current intensity) according to his/her individual sensitivity, which can vary from day to day or even over the period of the therapy.<br>Radiation: Radiotherapy<br>* Standard treatment for included patients<br>|
| Sham Comparator: Control<br>Treatment will be carried out twice a day (once before the RT session and 8h later) during 7 weeks. Each treatment takes 30 minutes. | Device: Sham<br>* Sham Earclip electrodes are electrodes that appear identical to functioning electrodes, however do not deliver any stimulation due to removed wiring.<br>Radiation: Radiotherapy<br>* Standard treatment for included patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer prognosis: tumor marker | CEA (µg/mL) | 7 weeks | 
| Cancer prognosis: inflammatory level | CRP (mg/mL) | 7 weeks | 
| Cancer prognosis: inflammatory level | cytokines: IL1, IL2, IL6 and IL8 (pg/mL) | 7 weeks | 
| Cancer prognosis: immunological factors | neutrophil count (x10³/mm³) | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health related Quality of Life | To assess the psychological well-being and quality of life of the patients during their radiotherapy treatment the EORTC QLQ-C30 questionnaire will be used. | 7 weeks |