Effect of Transcutaneous Auricular Vagal Nerve Stimulation on Acute Pancreatitis

NCT06998784 | Completed DMC

• 1 other identifier: KY20242424
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

Acute pancreatitis (AP), characterized by the sudden onset of pancreatic inflammation, is a frequent gastrointestinal emergency. Early suppression of the inflammatory response is critical to mitigate disease progression. When localized pancreatic inflammation progresses to systemic inflammation, triggering systemic inflammatory response syndrome (SIRS), the condition advances to moderate or severe AP, with mortality rates ranging from 10% to 40%. Additionally, early resumption of enteral nutrition reduces the risk of intra-abdominal infections and organ failure associated with AP. However, gastrointestinal dysfunction, which frequently manifests as gastroparesis or intestinal obstruction in severe cases , significantly complicates AP management by prolonging recovery time and compromising nutritional tolerance. Current early-phase management of AP remains suboptimal: anti-inflammatory strategies are predominantly limited to fluid resuscitation, while gastrointestinal function preservation is frequently underestimated. Consequently, effective therapies targeting both inflammatory suppression and gastrointestinal functional restoration in the early phase of AP are urgently needed. The central nervous system plays a pivotal role in regulating peripheral immune responses, with the vagal anti-inflammatory signaling pathway serving as a key efferent pathway of the inflammatory reflex. Animal studies have shown a protective effect of the vagal anti-inflammatory signaling pathway against AP. Specifically, vagus nerve stimulation (VNS) significantly reduced pancreatic injury and improved survival in mice with severe AP. Furthermore, VNS has shown therapeutic potential in animal models of sepsis, shock, and renal ischemia-reperfusion injury, conditions frequently associated with systemic inflammation in severe pancreatitis. These findings suggest that VNS may alleviate both local and systemic inflammatory responses, as well as their complications. Notably, prior clinical trial revealed that transcutaneous auricular VNS (taVNS) alleviated functional dyspepsia symptoms in adults, indicating its dual capacity for anti-inflammatory effects and gastrointestinal functional modulation. Based on this evidence, the investigators propose a randomized, sham-controlled trial to systematically evaluate the therapeutic efficacy of taVNS in patients with acute pancreatitis .

Conditions

Acute Pancreatitis (AP); Vagus Nerve Stimulations

Keywords

acute pancreatitis; vagus nerve stimulations; PAN-PROMISE

Outcome Measures

Primary Outcomes (1)

• Median treatment duration

  The number of treatment days required to reduce the PAN-PROMISE scores to 6. The PAN-PROMISE score (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis from an international proSpEctive cohort study) consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. Each symptom is rated on a scale of 0 to 10 points, where higher scores reflect greater symptom severity.

  Up to one week

Secondary Outcomes (4)

• PAN-PROMISE score during the study period

  1 week

• Responder rate

  1 week

• Biochemical Profiles

  at treatment days 3

• Median time from AP onset to enteral nutrition resumption

  an average of 1 week

Study Arms (2)

Treatment group

EXPERIMENTAL

Patients will receive taVNS at left tragus up to 7 days.

Device: taVNS

Sham-treatment group

SHAM COMPARATOR

Patients will receive sham-taVNS at left earlobe up to 7 days.

Device: Sham-taVNS

Interventions

taVNS DEVICE

Patients will receive taVNS at left tragus (a device developed by the Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education (School of Life Science and Technology, Xidian University), in collaboration with the Wearable BCI and Intelligent Rehabilitation Innovation Lab (Guangzhou Institute of Technology, Xidian University)) twice daily (morning and night) for 30 minutes per session over a period of up to 7 days. The stimulation parameters are as follows: * Duty circle: 30s "on" periods alternating with 30s "off" periods; * Frequency: 25 Hz; * Amplitude: 0-2 mA (adjusted to the maximum tolerated level for each patient); * Pulse width: 0.5 ms.

Treatment group

Sham-taVNS DEVICE

Patients will receive taVNS at left earlobe (a device developed by the Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education (School of Life Science and Technology, Xidian University), in collaboration with the Wearable BCI and Intelligent Rehabilitation Innovation Lab (Guangzhou Institute of Technology, Xidian University)) twice daily (morning and night) for 30 minutes per session over a period of up to 7 days. The stimulation parameters are as follows: \*Duty circle: 30s "on" periods alternating with 30s "off" periods; \*Frequency: 25 Hz; \*Amplitude: 0-2 mA (adjusted to the maximum tolerated level for each patient); \*Pulse width: 0.5 ms.

Sham-treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AP patients aged 18-80 years.
• PAN-PROMISE score ≥15 and no participation in any other clinical trials within the past 3 months.
• AP patients who presented to the emergency department no more than 24 hours after symptom onset and who had received a diagnosis no more than 8 hours before enrollment.

You may not qualify if:

• Patients with an APACHE II score≥8, a C-reactive protein (CRP) level \> 150 mg/L, or organ failure at baseline (shock, respiratory failure, or renal failure) were excluded.
• Presence of diseases or conditions different from AP that may interfere with the scale, for example, other causes of abdominal pain (especially acute cholecystitis), obstruction of the digestive tract (peptic pyloric stenosis, gastrointestinal anastomotic stenosis, diabetic gastroparesis, gastrointestinal neoplasia...), nausea-vomiting (brain tumour, chemotherapy...) or weakness (pre-existing anaemia with haemoglobin \<9 g/dL, heart failure or respiratory insufficiency associated with minimal effort dyspnoea, or domiciliary treatment with O2, advanced neoplasms or other debilitating diseases);
• Implanted cardiac pacemaker or other electronic devices;
• Prior treatment with transcutaneous auricular vagus nerve stimulation (taVNS);
• Known malignancy;
• Severe cardiovascular/cerebrovascular, hepatic, or renal diseases;
• Cognitive impairment, psychiatric disorders, or other conditions that may affect patient cooperation;
• Refusal to sign informed consent.

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (5)

The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA)

Shijiazhuang, Hebei, 050082, China

Location

Shaanxi Second People's Hospital

Xi'an, Shaanxi, 710000, China

Location

Xijing Hospital of Digestive Diseases

Xi'an, Shaanxi, 710032, China

Location

Department of Gastroenterology , Tangdu Hospital , Fourth Military Medical University

Xi'an, Shaanxi, 710038, China

Location

Department of Gastroenterology, 986 Hospital of Xijing Hospital, Fourth Military Medical University

Xi'an, Shaanxi, 710054, China

Location

Related Publications (7)

• Shi X, Zhao L, Luo H, Deng H, Wang X, Ren G, Zhang L, Tao Q, Liang S, Liu N, Huang X, Zhang X, Yang X, Sun J, Qin W, Kang X, Han Y, Pan Y, Fan D. Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study. Am J Gastroenterol. 2024 Mar 1;119(3):521-531. doi: 10.14309/ajg.0000000000002548. Epub 2023 Oct 3.

  PMID: 37787432 BACKGROUND

• Inoue T, Abe C, Sung SS, Moscalu S, Jankowski J, Huang L, Ye H, Rosin DL, Guyenet PG, Okusa MD. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through alpha7nAChR+ splenocytes. J Clin Invest. 2016 May 2;126(5):1939-52. doi: 10.1172/JCI83658. Epub 2016 Apr 18.

  PMID: 27088805 BACKGROUND

• Morishita K, Costantini TW, Eliceiri B, Bansal V, Coimbra R. Vagal nerve stimulation modulates the dendritic cell profile in posthemorrhagic shock mesenteric lymph. J Trauma Acute Care Surg. 2014 Mar;76(3):610-7; discussion 617-8. doi: 10.1097/TA.0000000000000137.

  PMID: 24553526 BACKGROUND

• Kelly MJ, Breathnach C, Tracey KJ, Donnelly SC. Manipulation of the inflammatory reflex as a therapeutic strategy. Cell Rep Med. 2022 Jul 19;3(7):100696. doi: 10.1016/j.xcrm.2022.100696.

  PMID: 35858588 BACKGROUND

• Mederos MA, Reber HA, Girgis MD. Acute Pancreatitis: A Review. JAMA. 2021 Jan 26;325(4):382-390. doi: 10.1001/jama.2020.20317.

  PMID: 33496779 BACKGROUND

• Xie J, Cai Y, Xu H, Peng Y, McArthur A. Early enteral nutrition support for patients with acute pancreatitis in the inpatient setting: a best practice implementation project. JBI Evid Implement. 2024 May 1;22(2):175-185. doi: 10.1097/XEB.0000000000000410.

  PMID: 38415812 BACKGROUND

• Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol. 2019 Aug;16(8):479-496. doi: 10.1038/s41575-019-0158-2.

  PMID: 31138897 BACKGROUND

MeSH Terms

Conditions

Pancreatitis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 31, 2025
• Study Start: May 15, 2025
• Primary Completion: November 20, 2025
• Study Completion: December 1, 2025
• Last Updated: March 31, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)