Data Sheet 1_A sham-controlled randomised trial evaluating the safety, acceptability, and efficacy of autonomic neuromodulation using transcutaneous vagal sensory stimulation in uncontrolled hypertensive patients: rationale and study design of the SCRATCH-HTN study.docx

BackgroundDespite the broad availability of antihypertensive drugs, approximately 40% of hypertensive patients fail to achieve the recommended blood pressure (BP) levels and may require alternative treatment(s). At present, renal denervation is the only proven non-pharmacological device-based alternative treatment available, but it is a costly, invasive, hospital-based procedure that is unlikely to be widely available. Transcutaneous autonomic neuromodulation (tAN)—if shown to be safe, acceptable, and efficacious—can offer a non-invasive, inexpensive, self-administered device-based innovative adjunct or alternative to pharmacological therapy.
MethodsSCRATCH-HTN is a double-blind, sham-controlled trial, with 63 participants randomised on a 2:1 basis to receive either tAN or sham-tAN treatment. Hypertensive patients on medication were included if they had elevated systo-diastolic BPs on daytime ambulatory BP monitoring (ABPM) [systolic BP (SBP) of ≥135 and <170 mmHg and mean daytime diastolic BP (DBP) of ≥85 and <115 mmHg]. Participants were trained to self-administer tAN therapy for 30 min every day for first 14 days and then once a week for 10 weeks. The primary endpoint was change in daytime ambulatory SBP from baseline to 3 months. Secondary endpoints included change in 24-h ambulatory and office SBP and DBP, BP variability, heart rate variability, quality of life, and sleep quality from baseline to end of treatment. Other exploratory outcomes included evaluation of impact on functional exercise (6-min walk test), structural and functional changes in the heart, cognitive function, and central blood pressures. A subgroup of patients underwent detailed autonomic functional assessment at the start and end of the study.
ConclusionThe SCRATCH-HTN trial is a phase 2a study testing the safety, acceptability, and potential efficacy of tAN treatment for improving blood pressure control in patients with elevated BP despite medication. It also explores the effects of tAN on sleep, exercise tolerance, heart rate variability, central BP, cardiac structure, and autonomic function. If effective, it could offer a transformative approach to hypertension management.

Study Protocol RegistrationClinicaltrials.gov, identifier NCT05179343 and ISRCTN (14509154).