Clinical trial NCT02519868: Chemical Block and Electrical Stimulation of the Carotid Body to Treat Refractory Hypertension
Official title: Chemical Block and Electrical Stimulation of the Carotid Body to Treat Refractory Hypertension
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Hypertension
Keywords: Neuromodulation
Local anaesthetics
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
First posted: 2015-08-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Blood pressure
timeFrame: 15 minutes after electrical block and 15 minutes after chemical block
Secondary outcomes:
measure: Heart rate
timeFrame: 15 minutes after each intervention
measure: Presence of paraesthesia
timeFrame: During the procedure
measure: Presence of dyspnea
timeFrame: During the procedure
measure: Presence of Claude-Bernard-Horner Syndrome
timeFrame: During the procedure
measure: Presence of hoarseness
timeFrame: During the procedure
measure: Presence of hematoma
timeFrame: During the procedure
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Department of Anesthesia, Centre Hospitalier Universitaire Vaudois and University of Lausanne
state: Vaud
Study officials:
affiliation: CHUV
name: Eric Albrecht, PD Dr
role: PRINCIPAL_INVESTIGATOR
References:
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citation: McBryde FD, Abdala AP, Hendy EB, Pijacka W, Marvar P, Moraes DJ, Sobotka PA, Paton JF. The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension. Nat Commun. 2013;4:2395. doi: 10.1038/ncomms3395.
citation: Alnima T, Scheffers I, De Leeuw PW, Winkens B, Jongen-Vancraybex H, Tordoir JH, Schmidli J, Mohaupt MG, Allemann Y, Kroon AA. Sustained acute voltage-dependent blood pressure decrease with prolonged carotid baroreflex activation in therapy-resistant hypertension. J Hypertens. 2012 Aug;30(8):1665-70. doi: 10.1097/HJH.0b013e3283551f10.