Efficacy and mechanisms of low-frequency TENS for common multimorbidity in older adults: protocol for a pilot randomized controlled trial

Background: Multimorbidity (co-occurrence of ≥2 chronic conditions) in older adults is a global health challenge, often managed with polypharmacy that carries risks of adverse events and drug-drug interactions. As a pilot randomized controlled trial (RCT), this study first aims to assess the feasibility of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) delivery in older adults with multimorbidity and estimate effect sizes for a subsequent definitive trial. Second, we examine the efficacy of Lo-TENS as an adjunct to routine clinical management for improving blood pressure, glycemic control, and lipid profiles, and explore the underlying autonomic nervous system (ANS) modulation mechanisms through analysis of heart rate variability and key inflammatory/metabolic biomarkers, which are hypothesized to mediate Lo-TENS's beneficial effects on clinical indicators. Methods: A pilot single-center, single-blinded, sham-controlled RCT will enroll 50 older adults (≥60 years) with multimorbidity (≥2 of EH, T2DM, hyperlipidemia). Participants will be randomly allocated (1,1) to receive Lo-TENS (2 Hz, 30 min/day, 5 days/week for 4 weeks) plus routine care or sham Lo-TENS plus routine care. Co-primary outcomes are office systolic blood pressure (SBP), fasting blood glucose (FBG), and low-density lipoprotein cholesterol (LDL-C) at post-intervention. Secondary outcomes include 24-h ambulatory BP, heart rate variability (HRV), inflammatory/metabolic biomarkers, and quality of life. Mechanistic analyses will explore mediation by ANS and inflammatory markers. Follow-up assessments will be conducted 4 weeks post-intervention. Discussion: This trial will provide evidence on the effectiveness of Lo-TENS on clinical outcomes in multimorbidity in older adults, and explore the underlying mechanisms through which Lo-TENS may alleviate the clinical indicators of multimorbidity, specifically by analyzing heart rate variability and key inflammatory and metabolic biomarkers. Trial registration: www.chictr.org.cn, identifier ChiCTR2400093956.