Neuromodulation of Cardiovascular Risks Associated With Cardiotoxic Chemotherapy

Study Overview
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Brief Summary
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This study is to determine if low level vagus nerve stimulation will lead to improvement in heart function, heart rate variation, and in the levels of certain chemical markers of inflammation in study participants' blood.

Detailed Description
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Patients will be asked to use a handheld electrical unit (stimulator) at home to deliver vagus nerve stimulation (low level stimulation) to one ear for a period of 1 hour for 14 days.

Official Title
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Neuromodulation of Cardiovascular Risks Associated With Cardiotoxic Chemotherapy: A First in Human Randomized Pilot Study. Neuromodulation in Cancer Study (OU-SCC-NCAN)

Conditions
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Breast Cancer, Lymphoma

Intervention / Treatment
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* Device: PARASYM neuromodulation device
* Device: PARASYM neuromodulation device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients (>50 years) with breast cancer or lymphoma, who have received anthracycline-based therapy (a cumulative dose of ≥ 200 mg/m2 Doxorubicin or bioequivalent dose of other anthracyclines) and/or HER2 antagonists within the last 60-90 days and have >= 1 of following additional criteria: previous chest radiation, type 2 diabetes mellitus, hypertension, current smoking, obesity (BMI ≥ 30), previous myocardial infarction or established atherosclerotic heart disease. Exclusion Criteria: atrial paced rhythm, history of seizure currently on treatment, history of vasovagal syncope, end stage liver or kidney disease.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 99 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized, sham controlled, double-blinded study of low-level tragus stimulation vs. sham treatment.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Self administration of Low Level Tragus Stimulation (LLTS; Placebo)<br>PARASYM neuromodulation device will be placed in a pre-determined position of one ear for 1 hour every day for 14 days. | Device: PARASYM neuromodulation device<br>* Patients with breast cancer or lymphoma who have undergone chemotherapy for their disease, will have tests to determine heart function. Patients will be asked to use a handheld electrical unit (stimulator) at home to deliver vagus nerve stimulation (low level stimulation) to a different position of one ear compared to the experimental arm for a period of 1 hour for 14 days. After approximately 14 days, patients will have the same tests that they had at the beginning of the study.<br>* Other names: Placebo;|
| Experimental: Self administration of LLTS<br>PARASYM neuromodulation device will be placed in a pre-determined position (different from that of the placebo) of one ear for 1 hour every day for 14 days. | Device: PARASYM neuromodulation device<br>* Patients with breast cancer or lymphoma who have undergone chemotherapy for their disease, will have tests to determine heart function. Patients will be asked to use a handheld electrical unit (stimulator) at home to deliver vagus nerve stimulation (low level stimulation) to a preset position of one ear for a period of 1 hour for 14 days. After approximately 14 days, patients will have the same tests that they had at the beginning of the study.<br>* Other names: Experimental;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of low-level tragus stimulation (LLTS) on global longitudinal strain (GLS) | An echocardiogram will be performed on patients at baseline and at follow up (14 days after start of intervention). The percentage change of GLS and left ventricular ejection fraction (LVEF) will be compared at baseline and follow up in patients receiving cardiotoxic chemotherapy. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of LLTS on autonomic tone | Measure change in autonomic tone by 15-minute Heart Rate Variability at baseline and follow up. (2 week) HRV has time and frequency domain numbers that are continuous variables from 0-100 and more. | 2 weeks | 
| Effects of LLTS on oxidative stress | Analyze markers of oxidative stress in serum collected from patients at baseline and at follow up. Serum will be analyzed for oxidative stress before and after use of the TENS device. Results are expressed in Units - continuous variable. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stimulation Device, Vagus Nerve Stimulator