Recruiting
Phase 4
Bacillus Subtilis and Enterococcus Faecium Probiotic Plus Lipid-Lowering Therapy for Hypertriglyceridemic Acute Pancreatitis: A Prospective RCT
Condition(s) studied
Hypertriglyceridemic Acute PancreatitisAcute Pancreatitis, Hypertriglyceridemia-inducedHyperlipidemia
Investigational drug(s) / intervention(s)
Live Combined Bacillus subtilis and Enterococcus faecium Enteric-coated Capsules (LCBE)Standard Care (in control arm)
Live Combined Bacillus subtilis and Enterococcus faecium Enteric-coated Capsules (LCBE): LCBE 500 mg (2 capsules) orally three times daily for 28 ± 2 days, initiated within 24 hours after confirmation of eligibility.
Standard Care (in control arm): Patients in the control group received standard care exclusively, in accordance with the 2021 Chinese Expert Consensus on the Emergency Diagnosis and Treatment of Hypertriglyceridemic Acute Pancreatitis. This regimen encompassed fenofibrate and low-molecular-weight heparin, alongside goal-directed fluid resuscitation. Comprehensive symptomatic and supportive therapies included somatostatin and ulinastatin infusions, proton pump inhibitor therapy, nutritional support, and analgesia management.
Study summary
Background: Hypertriglyceridemia-associated acute pancreatitis (HTG-AP) has become the second most common cause of acute pancreatitis in China, accounting for up to 42.4% of cases, with high recurrence rates and substantial disease burden. Disease severity and recurrence risk are potentially linked to triglyceride (TG) levels. Current lipid-lowering strategies have limitations in efficacy, onset speed, or safety. Increasing evidence suggests that gut microbiota dysbiosis and impaired intestinal barrier function contribute to lipid metabolism regulation and systemic inflammation in HTG-AP patients. Probiotic supplementation may offer a novel therapeutic approach by modulating gut microbiota, improving lipid metabolism, and alleviating inflammation.
Objective: To evaluate whether adjunctive treatment with Bacillus subtilis and Enterococcus faecium enteric-coated capsules (LCBE) reduces serum TG and inflammatory markers and improves clinical outcomes in mild to moderate HTG-AP patients.
Methods: This is a prospective, randomized, open-label, blinded endpoint (PROBE design), single-center, parallel-group clinical trial. A total of 180 eligible participants will be randomized 1:1 to the intervention group (standard therapy plus oral LCBE 500 mg three times daily for 28 days) or control group (standard therapy alone). The primary endpoints are serum TG, C-reactive protein (CRP), and interleukin-6 (IL-6) levels on day 5 post-intervention. Secondary endpoints include TG normalization rate (\<1.7 mmol/L), lipid profile, inflammatory markers, glucose metabolism parameters, gut microbiota composition, intestinal barrier integrity, symptom relief, length of hospital stay, healthcare costs, quality of life, and safety.
Expected Impact: This study aims to provide high-level evidence for probiotic adjunctive therapy in HTG-AP and to explore underlying mechanisms from the perspective of gut microbiota modulation.
Eligibility
Inclusion Criteria:
1. Meet at least two of the three characteristic criteria for AP:① Acute onset of persistent upper abdominal pain;② Serum amylase and/or lipase activity at least three times above the upper limit of normal;③ Imaging findings on CT, MRI, or abdominal ultrasonography.
2. Meet the diagnostic criteria for hypertriglyceridemia-associated acute pancreatitis (HTG-AP): fulfill the AP diagnostic criteria and concurrent hypertriglyceridemia (serum triglycerides ≥11.3 mmol/L or 5.65-11.3 mmol/L with lactescent serum), with exclusion of other common causes of AP such as cholelithiasis and alcoholism.
3. Admission within 72 hours of symptom onset.
4. Disease severity assessed as mild acute pancreatitis (MAP) within 48 hours of admission, defined by absence of organ dysfunction and absence of local or systemic complications.
5. Age between 18 and 65 years.
6. No history of allergy to microbiological agents.
7. Signed informed consent obtained.
Exclusion Criteria:
1. Concurrent biliary, alcoholic, or other etiologies of acute pancreatitis;
2. Acute exacerbation of chronic pancreatitis or pancreatic tumor;
3. Severe hypertriglyceridemia-associated acute pancreatitis, defined as: ① patients classified as moderately severe or severe AP according to the Expert Consensus on the Diagnosis and Treatment of Hypertriglyceridemic Acute Pancreatitis; ② within 48 hours, meeting any one of the following criteria: modified Marshall score ≥2, MCTSI score ≥4, APACHE II score ≥15, BISAP score ≥3, or Ranson score ≥3; patients meeting any of these criteria are excluded;
4. Severe hepatic or renal dysfunction (serum creatinine \>177 μmol/L or ALT \>150 U/L);
5. Active infection, malignancy, immunodeficiency, or requiring long-term use of immunosuppressants;
6. Diagnosed diabetes mellitus;
7. Pregnancy or breastfeeding;
8. History of lactose intolerance;
9. Use within 4 weeks prior to enrollment of antibiotics, probiotics, prebiotics, synbiotics, or other microbiological agents, as well as gastrointestinal motility drugs (e.g., domperidone, mosapride) or other medications that may significantly affect gut microbiota or gastrointestinal function.
Primary outcome measure(s)
- Mean Concentration of Serum Triglycerides (TG) in mmol/L at 5 ± 2 days. — Baseline through Day 5 (±2 days)
Blood samples will be collected after a minimum 8-hour fast. Serum triglycerides (TG) will be measured quantitatively using an enzymatic colorimetric assay on an automated clinical chemistry analyzer in the central laboratory of Xiamen University Zhongshan Hospital. The primary endpoint is the mean concentration of serum TG (in mmol/L) at the intervention visit occurring 5 ± 2 days after randomization. Values are presented as the mean (standard deviation, SD).
- Serum Concentration of C-Reactive Protein (CRP) at Day 5 (±2 days) — Baseline through Day 5 (±2 days)
Fasting venous blood samples will be collected at the Day 5 (±2 days) visit. Serum CRP will be quantified using a high-sensitivity immunoturbidimetric assay, and will be presented as Mean (Standard Deviation) in mg/L.
- Serum Concentration of Interleukin-6 (IL-6) at Day 5 (±2 days) — Baseline through Day 5 (±2 days)
Fasting venous blood samples will be collected at the Day 5 (±2 days) visit. Serum IL-6 will be measured via chemiluminescence immunoassay. Data will be presented as Mean (Standard Deviation) in pg/mL.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Department of Gastroenterology, Zhongshan Hospital, Xiamen University |
Xiamen |
Fujian |
Recruiting |
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