Transcutaneous Auricular Vagal Nerve Stimulation Alleviates Symptoms of Mild Acute Pancreatitis: A Multicenter Randomized Double-blind Sham-controlled Study

BACKGROUND AIMS: Vagus nerve stimulation (VNS) holds promise for modulating inflammation and gastrointestinal function, but its efficacy as an adjunctive therapy for acute pancreatitis (AP) remains unclear. This study aimed to investigate the protective effects of transcutaneous VNS (taVNS) in patients with AP. METHODS: Patients with mild acute pancreatitis (MAP) and a PAN-PROMISE score ≥15 were recruited from five tertiary hospitals in China. Patients were randomly assigned to receive taVNS or sham-taVNS plus standard care. Stimulation parameters were set as follows: pulse width 0.5 ms, frequency of 25 Hz, and amplitude ranging from 0.5 to 1.5 mA. Patients, care providers and outcome assessors remained blinded to treatment allocation throughout the study. The primary endpoint was the median time to achieve a PAN-PROMISE score ≤ 6. RESULTS: A total of 60 patients were randomized. The taVNS group had a shorter median time to reach a PAN-PROMISE score ≤ 6 than the sham-taVNS group (3.00 vs. 4.00 days; HR = 1.956, P = 0.002). The proportion of patients achieving a PAN-PROMISE score ≤ 6 within the first 3 days was significantly higher in the taVNS group than in the sham-taVNS group (50.00% vs. 13.33%, P = 0.002). taVNS was associated with a more significant improvement in the subscales of the PAN-PROMISE, including abdominal pain, abdominal distension, and dysphagia (all P < 0.05). By day 3, the taVNS group showed a greater reduction in CRP levels compared with the sham-taVNS group (-32.40 mg/L vs. 12.75 mg/L, P = 0.005). Adverse events were mild and did not differ between the groups. CONCLUSIONS: In patients with MAP, taVNS was associated with earlier symptom resolution and potential anti-inflammatory effects with a favorable safety profile ( ClinicalTrial.gov: NCT06998784).