Award Title: Evaluating the Safety, Acceptability and Efficacy of Autonomic neuromodulation using trans-cutaneous vagal stimulation in uncontrolled hypertensive patients (SCRATCH –HTN): a pilot study evaluating a novel noninvasive device-based strategy
Funder: Department of Health and Social Care

Abstract: Hypertension or high blood pressure (BP) is the leading cause of cardiovascular morbidity and mortality. Despite the widespread availability of antihypertensive drugs, nearly 40% of all treated patients fail to achieve the recommended level of BP. Several factors contribute, including drug-resistance, poor adherence to prescribed medications, and/or drug-intolerance. For the uncontrolled hypertensive patients, the lack of an alternative therapy is an urgent unmet clinical need. One potential strategy is to target the autonomic imbalance that many hypertensive patients exhibit. Exploiting this therapeutic pathway and taking advantage of recent advances in device-based neuromodulation, we developed a novel device-based solution for hypertension treatment. The device works by algorithm-based electrical stimulation of the specific region of the external ear (tragus), innervated by the branches of several cranial (Vth, Xth) and spinal nerves (C2/3). This form of transcutaneous autonomic neuromodulation (tAN) non-invasively redresses the autonomic imbalance leading to a reduction in sympathetic activity. A proof-of-concept study involving drug-resistant/uncontrolled hypertensive patients demonstrated that our proprietary tAN algorithm effectively reduces the systolic BP in the drug-resistant cohort by >10mmHg, with the beneficial effect lasting for >1 month after the discontinuation of therapy.   This project aims to develop the tAN into an effective treatment strategy for hypertension by 1) undertaking a randomized, double-blind, sham-controlled study to evaluate the safety, acceptability and efficacy of tAN in hypertension; 2) building a pre-production tAN device compliant with the regulatory medical, safety and electrical standards; 3) undertaking a health economics study to determine the cost implications and adoption challenges of the technology.   By the completion of the project, we expect to have the clinical data, ISO13485 quality management system and a medical device regulations-compliant device ready for regulatory approval within 6 months. If efficacious, this device is a potential game-changer which provides a non-invasive, self-administered, low-cost hypertension treatment option.

Lay Abstract: Raised blood pressure (BP) or hypertension is the single most preventable cause of stroke, heart attack, heart failure, cardiovascular death, and is the leading risk factor for developing dementia, and kidney failure. By lowering BP the combined risk of associated disability and death can be reduced by more than a half. However, despite the widespread availability of antihypertensive medications, ~40% of all treated hypertensive patients fail to achieve the recommended level of BP (  The brain subconsciously controls the heart and blood pressure by sending commands via specialized nerves. In hypertensive individuals, there is an imbalance in the activities of these nerves and currently available medical treatments do not target them effectively. Studies have shown that non-pharmacological approaches can potentially redress this imbalance, and thereby reduce BP in these patients. Several companies are working on solutions using this approach, all involve invasive devices and/or in-hospital procedures that are costly. In contrast, the new solution is non-invasive, does not require hospital procedures/stay, and of low cost. Results of our proof-of-concept study show that using a very specific electrical stimulation algorithm, applied non-invasively to the skin of the outer ear (this approach is called transcutaneous autonomic neuromodulation) BP can be effectively reduced in drug-resistant patients.  The aim of this project is to develop this new technology into a clinical treatment of hypertension ready for regulatory approval and clinical adoption. We will: 1) undertake a clinical study designed to determine the treatment efficacy in a large cohort of hypertensive patients; 2) design and build a pre-production prototype device in compliance with the regulatory standards; 3) undertake a health economics study and to develop an effective strategy to facilitate adoption of the technology by the NHS.  We have set-up a strong PPI initiative and interviewed patients. All interviewed patients considered this solution to be highly preferable to drugs. If using the new method the BP is reduced by >10 mmHg in just the drug-resistant hypertensive population, it would save the NHS >£500m in annual costs by reducing the incidents of associated strokes, coronary heart disease and kidney failures. It is expected that the treatment of high blood pressure will be regulatory approved and available for clinical use within 6 months and to become a recommended NICE intervention for the treatment of hypertension within 5 years after completion of the project.

Research Activity Codes: 6.3 MEDICAL DEVICES
Health Categories: CARDIOVASCULAR