Effect of Bacillus Subtilis and Enterococcus Faecium Combination Therapy Combined With Conventional Lipid-Lowering Treatment on Triglyceride Levels in Patients With Hypertriglyceridemic Acute Pancreatitis: A Prospective Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Mean Concentration of Serum Triglycerides (TG) in mmol/L at 5 ± 2 days.
研究概览
简要总结
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.
详细描述
Rationale:
Timely reduction of serum TG is critical for improving prognosis in HTG-AP. However, conventional therapies-including fibrates, insulin, heparin, and blood purification-have limitations related to onset speed, invasiveness, cost, and adverse effects. Preclinical and clinical studies suggest that Bacillus subtilisand Enterococcus faecium(LCBE) can improve lipid metabolism, restore gut microbial balance, enhance intestinal barrier function, and reduce systemic inflammation. Nevertheless, robust prospective RCT evidence focusing on TG dynamics in HTG-AP remains lacking.
Study Population and Setting:
Adult patients (18-65 years) diagnosed with mild HTG-AP (serum TG ≥11.3 mmol/L or 5.65-11.3 mmol/L with lactescent serum) within 72 hours of symptom onset will be enrolled from the Department of Gastroenterology, Zhongshan Hospital, Xiamen University. Patients with severe or moderately severe AP, other etiologies of AP, significant organ dysfunction, pregnancy, immunosuppression, diabetes mellitus, lactose intolerance, or recent use of antibiotics/probiotics will be excluded.
Intervention and Follow-up:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Care Provider, Outcomes Assessor)
盲法说明
Due to the nature of probiotic administration, participants and investigators are unmasked; however, outcome assessors (nurses performing VAS assessment) and statisticians are blinded to group allocation
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
- •Admission within 72 hours of symptom onset.
- •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.
- •Age between 18 and 65 years.
- •No history of allergy to microbiological agents.
- •Signed informed consent obtained.
排除标准
- •Concurrent biliary, alcoholic, or other etiologies of acute pancreatitis;
- •Acute exacerbation of chronic pancreatitis or pancreatic tumor;
- •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;
- •Severe hepatic or renal dysfunction (serum creatinine >177 μmol/L or ALT >150 U/L);
- •Active infection, malignancy, immunodeficiency, or requiring long-term use of immunosuppressants;
- •Diagnosed diabetes mellitus;
- •Pregnancy or breastfeeding;
- •History of lactose intolerance;
- •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.
结局指标
主要结局
Mean Concentration of Serum Triglycerides (TG) in mmol/L at 5 ± 2 days.
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- Mean Concentration of Serum Triglycerides (TG) in mmol/L at 14 ± 2 days(Baseline through Day 14 (±2 days))
- Mean Concentration of Serum Triglycerides (TG) in mmol/L at 28 ± 2 days(Baseline through Day 28 (±2 days))
- Serum Concentration of C-Reactive Protein (CRP) at Day 14 (±2 days)(Baseline through Day 14 (±2 days))
- Serum Concentration of C-Reactive Protein (CRP) at Day 28 (±2 days)(Baseline through Day 28 (±2 days))
- Percentage of Participants Achieving Serum Triglyceride (TG) Normalization (<1.7 mmol/L) at Day 5 (±2 days)(Baseline through Day 5 (±2 days))
- Percentage of Participants Achieving Serum Triglyceride (TG) Normalization (<1.7 mmol/L) at Day 14 (±2 days)(Baseline through Day 14 (±2 days))
- Percentage of Participants Achieving Serum Triglyceride (TG) Normalization (<1.7 mmol/L) at Day 28 (±2 days)(Baseline through Day 28 (±2 days))
- Percentage Change from Baseline in Serum Triglyceride (TG) Concentration at Day 5 (±2 days)(Baseline through Day 5 (±2 days))
- Percentage Change from Baseline in Serum Triglyceride (TG) Concentration at Day 14 (±2 days)(Baseline through Day 14 (±2 days))
- Percentage Change from Baseline in Serum Triglyceride (TG) Concentration at Day 28 (±2 days)(Baseline through Day 28 (±2 days))
- Percentage Change from Baseline in Serum C-Reactive Protein (CRP) at Day 5 (±2 days)(Baseline through Day 5 (±2 days))
- Percentage Change from Baseline in Serum C-Reactive Protein (CRP) at Day 14 (±2 days)(Baseline through Day 14 (±2 days))
- Percentage Change from Baseline in Serum C-Reactive Protein (CRP) at Day 28 (±2 days)(Baseline through Day 28 (±2 days))
- Percentage Change from Baseline in Serum Interleukin-6 (IL-6) at Day 5 (±2 days)(Baseline through Day 5 (±2 days))
- Change from Baseline in Gut Microbiota Alpha and Beta Diversity Indices Assessed by 16S rRNA Sequencing(Baseline through Day 28 (±2 days))
- Change from Baseline in Serum Intestinal Barrier Biomarkers (D-lactate, Endotoxin, DAO, Zonulin)(Baseline through Day 28 (±2 days))
研究者
Jianyin Zhou
Principal Investigator
Zhongshan Hospital Xiamen University