Chemical Block and Electrical Stimulation of the Carotid Body to Treat Refractory Hypertension

Study Overview
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Brief Summary
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High blood pressure, also referred to as hypertension, affects about 65 million people in the United States alone. Approximately 25 percent of people with hypertension cannot control their high blood pressure, despite the use of multiple medications. Recently, new evidence has demonstrated that the carotid body (CB) plays a role in essential refractory hypertension, possibly due to a deregulated, enhanced activity of this organ. Animal studies showed that CB de-afferentiation, through carotid sinus nerve denervation, leads to a long-term stable drop in blood pressure in spontaneously hypertensive rats. De-afferentiation may be performed either by injecting local anesthetics or by electrical stimulation. Both techniques are daily used in the operating theater to anesthetize nerves for a wide range of surgical procedures. We hypothesize that blocking CB with local anesthetics will result in a drop of the blood pressure in refractory hypertensive patients. We also want to test the idea that stimulating the CB with an electrical current will mislead the CB and will also result in a drop of the blood pressure.

Detailed Description
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High blood pressure, also referred to as hypertension, affects about 65 million people in the United States alone. Approximately 25 percent of people with hypertension cannot control their high blood pressure, despite the use of multiple medications. Recently, new evidence has demonstrated that the carotid body (CB) plays a role in essential refractory hypertension, possibly due to a deregulated, enhanced activity of this organ. Animal studies showed that CB de-afferentiation, through carotid sinus nerve denervation, leads to a long-term stable drop in blood pressure in spontaneously hypertensive rats. It has been further shown that hypertonicity of the CB leads to a sympathetic hyper-excitation in SH rats and causes an increased vasomotor tone, which in turn contributes to hypertension. The increased knowledge about the role of the CB in essential hypertension has lead to the development of an implantable (via open surgery) pulse generator, which lead to significant decrease in blood pressure at 12 months. One-year results from 13 patients showed a 39 mmHg average decrease in systolic blood pressure and a 26 mmHg average decrease in diastolic blood pressure in early reports. Beside, the procedure is invasive and requires surgery under general anesthesia. De-afferentiation may be performed either by injecting local anesthetics or by electrical stimulation. Both techniques are daily used in the operating theater to anesthetize nerves for a wide range of surgical procedures. We hypothesize that blocking CB with local anesthetics will result in a drop of the blood pressure in refractory hypertensive patients. We also want to test the idea that stimulating the CB with an electrical current will mislead the CB and will also result in a drop of the blood pressure. Preliminary results will shed some light on the mechanism of action of the CB in refractory hypertension and will open the way to new therapeutical approaches such as development of new implantable devices through a transcutaneous approach.

Official Title
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Chemical Block and Electrical Stimulation of the Carotid Body to Treat Refractory Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Device: Electrical block
* Device: Chemical block


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years of age, inclusive; blood pressure not controlled despite 3 different anti-hypertensive drugs; minimal body weight of 70 kg. Exclusion Criteria: history of neck surgery or radiotherapy; secondary hypertension; contraindications to regional anesthesia (e.g., allergy to local anesthetics, coagulopathy, bleeding diathesis, malignancy or infection in the area); pregnancy; severe respiratory disease; inability to understand the informed consent and demands of the study; patient refusal.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm<br>Patients will have both interventions: electrical stimulation followed by chemical stimulation | Device: Electrical block<br>* Nerve stimulator switched on at an intensity of 5 mA for 15 minutes, with the needle tip positioned close to the carotid bifurcation with the aid of the echography<br>Device: Chemical block<br>* Injection of lidocaine 1%, 15 mLs, with the needle tip positioned close to the carotid bifurcation, with the aid of the echography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure |  | 15 minutes after electrical block and 15 minutes after chemical block | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate |  | 15 minutes after each intervention | 
| Presence of paraesthesia |  | During the procedure | 
| Presence of dyspnea |  | During the procedure | 
| Presence of Claude-Bernard-Horner Syndrome |  | During the procedure | 
| Presence of hoarseness |  | During the procedure | 
| Presence of hematoma |  | During the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuromodulation, Local anaesthetics