Clinical trial NCT06998784: Effect of Transcutaneous Auricular Vagal Nerve Stimulation on Acute Pancreatitis
Official title: Effect of Transcutaneous Auricular Vagal Nerve Stimulation on Acute Pancreatitis: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Acute Pancreatitis (AP)
Vagus Nerve Stimulations
Keywords: acute pancreatitis
vagus nerve stimulations
PAN-PROMISE
Lead sponsor: Air Force Military Medical University, China
Sponsor class: OTHER
First posted: 2025-05-31
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 .


Eligibility criteria: Inclusion Criteria:

1. AP patients aged 18-80 years.
2. PAN-PROMISE score ≥15 and no participation in any other clinical trials within the past 3 months.

Exclusion Criteria:

1. 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);
2. Implanted cardiac pacemaker or other electronic devices;
3. Prior treatment with transcutaneous auricular vagus nerve stimulation (taVNS);
4. Known malignancy;
5. Severe cardiovascular/cerebrovascular, hepatic, or renal diseases;
6. Cognitive impairment, psychiatric disorders, or other conditions that may affect patient cooperation;
7. Refusal to sign informed consent.

Primary outcomes:
measure: Median treatment duration
timeFrame: Up to one week
Secondary outcomes:
measure: PAN-PROMISE score during the study period
timeFrame: 1 week
measure: Responder rate
timeFrame: 1 week
measure: Biochemical Profiles
timeFrame: at treatment days 3
measure: Median time from AP onset to enteral nutrition resumption
timeFrame: through study completion, an average of 1 week
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xijing Hospital of Digestive Diseases
state: Shaanxi
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Mederos MA, Reber HA, Girgis MD. Acute Pancreatitis: A Review. JAMA. 2021 Jan 26;325(4):382-390. doi: 10.1001/jama.2020.20317.
citation: 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.
citation: 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.