High-Intensity Transcranial Alternating Current Stimulation (Hi-tACS) for Hypertension: A Randomized Controlled Trial

Hypertension is a highly prevalent cardiovascular disease and a major risk factor for stroke, heart failure, and kidney disease. Many patients continue to have poorly controlled blood pressure despite standard medication, which may be due to excessive activity of the central sympathetic nervous system and poor long-term compliance. Conventional antihypertensive drugs mainly act on peripheral targets and lack regulation of the brain-heart axis, leaving a large clinical need for safe, non-pharmacological adjuvant treatments.

High-intensity transcranial alternating current stimulation (Hi-tACS) is a non-invasive neuromodulation technique that can modulate central autonomic networks and normalize sympathetic-parasympathetic balance. Recent studies and our preliminary data suggest that 77.5 Hz, 15 mA Hi-tACS may safely reduce blood pressure in individuals with elevated baseline levels. Therefore, we hypothesize that Hi-tACS can lower blood pressure in patients with primary hypertension by regulating brain autonomic function and reducing sympathetic overactivity.

This study aims to evaluate the efficacy and safety of Hi-tACS in adults with primary hypertension, explore its underlying neural and physiological mechanisms, and provide high-quality evidence for a new non-pharmacological approach to hypertension management.

Inclusion criteria

• Clinical diagnosis of primary hypertension (Grade 1-3) as defined by the Chinese Hypertension Guidelines (Revised Edition 2024).
• For females of childbearing potential, agreement to use contraception during the study.
• Willing and able to comply with study procedures and provide written informed consent.

Exclusion criteria

• Women who are pregnant, breastfeeding, or planning pregnancy during the study period.
• Resistant hypertension (blood pressure uncontrolled despite adherence to ≥3 antihypertensive drugs of different classes at optimal doses, including a diuretic ), or known secondary hypertension.
• History of severe cardiovascular or cerebrovascular disease (e.g., myocardial infarction, stroke, heart failure NYHA Class III-IV) within the past 6 months, or severe hepatic or renal dysfunction (defined as ALT/AST >3× upper limit of normal [ULN], or eGFR <30 mL/min/1.73 m²).
• Uncontrolled sleep apnea syndrome, active infectious diseases, chronic wasting diseases, or significant cognitive impairment.
• Current major psychiatric disorder as assessed by the Mini-International Neuropsychiatric Interview (M.I.N.I.).
• Contraindications to tACS or MRI: implanted electronic devices, intracranial metal implants, or known history of seizures.
• Skin lesions, eczema, or broken skin at the intended electrode placement sites.
• Participation in another clinical trial involving an investigational product or device within 30 days prior to screening.
• Any condition that, in the opinion of the investigator, would jeopardize the patient's safety or compliance with the study protocol, or interfere with data interpretation.