Low-Frequency Electroacupuncture versus Sham Electroacupuncture for Diabetic Peripheral Neuropathy: Study Protocol for a Randomized Controlled Trial.

Background: Diabetic peripheral neuropathy (DPN) is a prevalent and disabling complication, with over 50% of diabetic patients affected. Current pharmacologic therapies are limited by adverse effects, highlighting the need for safer alternatives. Preliminary evidence suggests that low-frequency (2 Hz) electroacupuncture (EA) may be beneficial, but high-quality clinical trials investigating its mechanisms are lacking. Methods and Analysis: This prospective, randomized, sham-controlled trial will enroll 92 patients with DPN, who will be randomly allocated in a 1:1 ratio to receive 6 weeks of treatment with either active 2 Hz EA or sham EA. The primary outcomes are overall response rate and lower-limb nerve conduction velocity (NCV). Secondary outcomes include pain intensity assessed using the Visual Analog Scale (VAS), quality of life scores, and serum biomarkers measured by enzyme-linked immunosorbent assay (ELISA), namely nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). All statistical analyses will be conducted according to the intention-to-treat (ITT) principle. Conclusion: This study is expected to provide clinical and mechanistic evidence for the potential role of standardized low-frequency EA as a non-pharmacological treatment option for DPN. Trial Registration: ClinicalTrials.gov Identifier: NCT07551726.