Efficacy and Safety of Non Invasive Vagal Stimulation to Prevent Chemotherapy-induced Nausea

Study Overview
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Brief Summary
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Despite pharmaceutical innovations, chemotherapy induced nausea is frequent and largely participating to alter our patients quality of life. Non invasive vagal stimulation is approved in other health issues, for example in headache or gastroparesis, with a reported benefit on nausea. This study aims to analyse if a non invasive vagal stimulation could better prevent chemotherapy induced nausea, in addition to standard treatment, in breast cancer patients treated with cyclophosphamide and anthracycline.

Detailed Description
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Despite pharmaceutical innovations, chemotherapy induced nausea is frequent and largely participating to alter our patients quality of life. Non invasive vagal stimulation is approved in other health issues, for example in headache or gastroparesis, with a reported benefit on nausea. This study aims to analyse if a non invasive vagal stimulation could better prevent chemotherapy induced nausea, in addition to standard treatment, in breast cancer patients treated with cyclophosphamide and anthracycline.

Official Title
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Efficacy and Safety of Non Invasive Vagal Stimulation to Prevent Chemotherapy-induced Nausea in Patients With Breast Cancer Receiving Anthracycline and Cyclophosphamide Chemotherapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: non invasive auricular vagal stimulation
* Drug: usual medical treatment
* Device: sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) status 0 to 2 patient with breast cancer planned to receive Anthracycline and Cyclophosphamide chemotherapy informed consent compliance expected social security affiliation Exclusion Criteria: nausea or vomiting 24h or less, before inclusion Antiemetic drug intake in the last 72h before inclusion Central nervous system metastasis Daily alcohol intake Prior chemotherapy Cardiac arrythmia, severe heart failure Device for sleep apnea History of arterial or venous thrombosis, or thrombophlebitis Vagotomy Vagal stimulation ongoing Skin disease on the stimulation zone Cochlear implant next to the stimulation zone Unable to use the vagal stimulation device due to left ear unusual shape Pregnant or breastfeeding women, or women of childbearing age without effective contraception Documented allergy or contraindication to one of the antiemesis drugs required in the study Protected adults (individuals under guardianship by court order) Unable to read or write

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: one control arm and one intervention arm
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention<br>standard anti emetic treatment use of non invasive vagal stimulation twice a day from the day before chemotherapy till 4 days after, with a transcutaneous auricular device. This stimulation is to be done for the three first cycles of chemotherapy. | Device: non invasive auricular vagal stimulation<br>* Stimulation twice a day, beginning the day before until the fourth day after chemotherapy, for the three first chemotherapy cycles<br>Drug: usual medical treatment<br>* Standard anti emetic treatments to prevent emesis due to chemotherapy<br>|
| Sham Comparator: control<br>standard anti emetic treatment use of non invasive vagal stimulation twice a day from the day before chemotherapy till 4 days after, with a transcutaneous auricular sham device. This stimulation is to be done for the three first cycles of chemotherapy. | Drug: usual medical treatment<br>* Standard anti emetic treatments to prevent emesis due to chemotherapy<br>Device: sham stimulation<br>* Stimulation twice a day, beginning the day before until the fourth day after chemotherapy, for the three first chemotherapy cycles, with a sham device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with significant nausea after the first chemotherapy cycle | Nausea severity is graded daily from Day 1 (day of chemotherapy) to Day 5, using a numeric scale from 0 to 10. It is a patient reported outcome, patients using a diary. Significant nausea is a score of 2 or more. | 2 to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with significant nausea after the second and the third chemotherapy cycle. | Same measurement at the second and the third chemotherapy. And global score considering the three cycles together. | 7 to 12 weeks | 
| Percentage of patients that did not vomit or use rescue emesis medication, from the first cycle of chemotherapy to day 5 after the third chemotherapy cycle. | Percentage of patients without any vomiting, or rescue emesis medication use, from first to third chemotherapy | 7 to 12 weeks | 
| Percentage of non planned visit to emergency care unit or general practioner or oncologist due to emesis, measured for the three first chemotherapy cycles. | To measure complication due to emesis from the first cycle of chemotherapy to day 5 after the third chemotherapy cycle | 7 to 12 weeks | 
| Percentage of non anticipated hydratation with IV fluids measured for the three first chemotherapy cycles. | To measure complication due to emesis from the first cycle of chemotherapy to day 5 after the third chemotherapy cycle | 7 to 12 weeks | 
| Percentage of hospitalisations for emesis measured for the three first chemotherapy cycles. | To measure complication due to emesis from the first cycle of chemotherapy to day 5 after the third chemotherapy cycle | 7 to 12 weeks | 
| quality of life measurement using international validated questionnaire EORTC QLQ-C30 (quality of life questionnaire -C30), EORTC QLQ-BR23 (quality of life questionnaire for breast cancer), completed at the first three cycles | patient reported outcome measure, using international validated questionnaires and patient diaries | 9 to 15 weeks | 
| number and type of side effect during vagal stimulation safety | report of any side effect, based on patient declaration | 7 to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea, non invasive vagal stimulation, chemotherapy, breast cancer