Bacillus Subtilis and Enterococcus Faecium Probiotic Plus Lipid-Lowering Therapy for Hypertriglyceridemic Acute Pancreatitis: A Prospective RCT

NCT07720232 | Recruiting Phase 4

• 1 other identifier: XUZH20260005
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypertriglyceridemic Acute Pancreatitis; Acute Pancreatitis, Hypertriglyceridemia-induced; Hyperlipidemia

Keywords

Hypertriglyceridemic Acute Pancreatitis; Probiotics; Bacillus subtilisand Enterococcus faecium; LCBE

Outcome Measures

Primary Outcomes (3)

• Mean Concentration of Serum Triglycerides (TG) in mmol/L at 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).

  Baseline through Day 5 (±2 days)

• Serum Concentration of C-Reactive Protein (CRP) at 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.

  Baseline through Day 5 (±2 days)

• Serum Concentration of Interleukin-6 (IL-6) at 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.

  Baseline through Day 5 (±2 days)

Secondary Outcomes (16)

• 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)

Other Outcomes (7)

• Time to Abdominal Pain Relief

  From randomization up to Day 28 (±2 days)

• Time to Successful Oral Feeding

  From randomization up to Day 28 (±2 days)

• Length of Hospital Stay

  From admission to discharge, up to Day 28 (±2 days)

Study Arms (2)

Standard Care combined LCBE

EXPERIMENTAL

LCBE refers to live combined Bacillus subtilis and Enterococcus faecium enteric-coated capsules. The dosage and treatment duration are as follows: LCBE 500 mg (2 capsules) administered orally three times daily for 28 ± 2 days, initiated within 24 hours after confirmation of eligibility. Standard care was administered 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. Additional symptomatic and supportive therapies included somatostatin and ulinastatin administration, proton pump inhibitor therapy, nutritional support, and analgesia management.

Drug: Live Combined Bacillus subtilis and Enterococcus faecium Enteric-coated Capsules (LCBE); Drug: Standard Care (in control arm)

Standard Care Only

ACTIVE COMPARATOR

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.

Drug: Standard Care (in control arm)

Interventions

Standard Care (in control arm) DRUG

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.

Standard Care Only; Standard Care combined LCBE

Live Combined Bacillus subtilis and Enterococcus faecium Enteric-coated Capsules (LCBE) DRUG

LCBE 500 mg (2 capsules) orally three times daily for 28 ± 2 days, initiated within 24 hours after confirmation of eligibility.

Also known as: Meichangan

Standard Care combined LCBE

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jianyin Zhou: lead

Study Sites (1)

Department of Gastroenterology, Zhongshan Hospital, Xiamen University

Xiamen, Fujian, 361004, China

RECRUITING

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MeSH Terms

Conditions

Pancreatitis; Hyperlipidemias

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Xu Hongzhi PhD

CONTACT

86-0592-2292232; xuhongzhi@xmu.edu.cn

Liu Yunpeng PhD

CONTACT

86-0592-2292232; liuyunpeng-84@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: July 22, 2026
• Study Start: January 18, 2026
• Primary Completion (Estimated): January 18, 2028
• Study Completion (Estimated): February 18, 2029
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 12 months after publication, ending 36 months after publication.
• Access Criteria: With whom? Researchers who provide a methodologically sound proposal, approved by an independent review committee. How to request? Email to corresponding author; data sharing agreement required. Access criteria ? Approval by the Data Access Committee of Dept. of Gastroenterology, Zhongshan Hospital, Xiamen University.

Locations

CN (1)