Acute Pancreatitis (AP), Vagus Nerve Stimulations
Conditions
Keywords
acute pancreatitis, vagus nerve stimulations, PAN-PROMISE
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 .
Interventions
DEVICEtaVNS
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.
DEVICESham-taVNS
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.
Sponsors
Air Force Military Medical University, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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. 3. 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.
Exclusion criteria
1. 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. 2. 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); 3. Implanted cardiac pacemaker or other electronic devices; 4. Prior treatment with transcutaneous auricular vagus nerve stimulation (taVNS); 5. Known malignancy; 6. Severe cardiovascular/cerebrovascular, hepatic, or renal diseases; 7. Cognitive impairment, psychiatric disorders, or other conditions that may affect patient cooperation; 8. Refusal to sign informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median treatment duration | Up to one week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PAN-PROMISE score during the study period | 1 week | Change from baseline in PAN-PROMISE score during the study period.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. |
| Responder rate | 1 week | Proportion of patients with PAN-PROMISE score reduced 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. |
| Biochemical Profiles | at treatment days 3 | Mean serum IL-6 concentration at treatment days 3 |
| Median time from AP onset to enteral nutrition resumption | an average of 1 week | Enteral nutrition (EN) resumption refers to nutritional intake via oral or jejunal tube routes following gastrointestinal functional recovery. |
Countries
China
Outcome results
None listed