Transcutaneous Auricular Vagus Nerve Stimulation Device in CKD Population

Study Overview
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Brief Summary
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The purpose of this pilot interventional study is to collect preliminary data on the application of a transcutaneous auricular vagal nerve stimulation (taVNS) device in patients with chronic kidney disease (CKD). This data will enhance understanding of the short-term safety, tolerability and effects of this novel therapeutic approach in the setting of CKD. The primary aims are to investigate the feasibility of the protocol and generate preliminary signals of efficacy and tolerability for two different doses of vagal nerve stimulation. The pilot estimates will be used to design a larger scale study that may lead to potentially targeted interventions to reduce cardiovascular (CV) mortality in the CKD population.

Official Title
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A Single Center Pilot Study on the Use of a Transcutaneous Auricular Vagus Nerve Stimulation Device in CKD Population

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Device: Transcutaneous electrical nerve stimulation unit (TENS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Individual 18-80 years of age with CKD stage 3-5 (eGFR <60 mL/min/1.73m2) on most recent outpatient labs. Exclusion Criteria: Pacemaker dependent Prisoners Pregnant women. A pregnancy test will be offered if a subject is concerned about being pregnant. Not capable of informed consent Know autonomic function disorder (e.g. Parkinson's disease with autonomic dysfunction) ICD or PPM precluding assessment of heart rate variability (e.g. chronic atrial fibrillation) Recent myocardial infarction (4 weeks or less) Maintenance dialysis Epilepsy Patients on labetalol (labetalol will interfere with catecholamine measurements) Patients with diabetes At least 50% of cohort must not be on beta blockers. This will help to distinguish the confounding effects of beta blockers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention A<br>Participants will receive 15 minutes of taVNS after an initial 15 minute rest-period and a 15 minute baseline measurement period. For participants assigned to Intervention A, the pulse width = 250 μs, and frequency = 50 Hz. | Device: Transcutaneous electrical nerve stimulation unit (TENS)<br>* The TENS unit will be applied to participants' right ear at the cymba conchae. The dose is dependent on which arm (Intervention A or Intervention B) the participant is assigned to. Participants will undergo 15 minutes of vagal nerve stimulation.<br>* Other names: TENS Device 7000;|
| Experimental: Intervention B<br>Participants will receive 15 minutes of taVNS after an initial 15 minute rest-period and a 15 minute baseline measurement period. For participants assigned to Intervention B, the pulse width = 300 μs, frequency = 25 Hz. | Device: Transcutaneous electrical nerve stimulation unit (TENS)<br>* The TENS unit will be applied to participants' right ear at the cymba conchae. The dose is dependent on which arm (Intervention A or Intervention B) the participant is assigned to. Participants will undergo 15 minutes of vagal nerve stimulation.<br>* Other names: TENS Device 7000;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate Variability (HRV) at Baseline | HRV is the variation in the time interval between heartbeats. | Day 1 (15 minutes prior to administration of intervention) | 
| HRV at Post-Intervention | HRV is the variation in the time interval between heartbeats. | Day 1 (15 minutes Post-Intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with at least a 20% change in HRV from baseline to post-intervention | The percentage of participants whose measured HRV changes by more than 20% from the baseline measurement to the post-intervention measurement. | Day 1 (Up to 15 Minutes Post-Intervention) | 
| Blood Pressure at Baseline | Blood pressure measured continuously for 15 minutes prior to intervention. | Day 1 (15 minutes prior to administration of intervention) | 
| Blood Pressure at Post-Intervention | Blood pressure measured continuously for 15 minutes post-intervention. | Day 1 (15 minutes Post-Intervention) | 
| Spontaneous Baroreceptor Sensitivity (BRS) at Baseline | Spontaneous BRS is defined as the change in interbeat interval (IBI) in milliseconds per unit change in blood pressure. | Day 1 (15 minutes prior to administration of intervention) | 
| Spontaneous BRS at Post-Intervention | Spontaneous BRS is defined as the change in interbeat interval (IBI) in milliseconds per unit change in blood pressure. | Day 1 (15 minutes Post-Intervention) | 
| Heart Rate at Baseline |  | Day 1 (15 minutes prior to administration of intervention) | 
| Heart Rate at Post-Intervention |  | Day 1 (15 minutes Post-Intervention) |