Bacillus Subtilis and Enterococcus Faecium Probiotic Plus Lipid-Lowering Therapy for Hypertriglyceridemic Acute Pancreatitis: A Prospective RCT
18. juli 2026 oppdatert av: Jianyin Zhou
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
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.
Studieoversikt
Status
Rekruttering
Forhold
Detaljert beskrivelse
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:
Participants will receive standard care according to the 2021 Chinese Expert Consensus on Emergency Management of HTG-AP, including fenofibrate, low-molecular-weight heparin, fluid resuscitation, somatostatin, ulinastatin, proton-pump inhibitors, nutritional support, and pain management. In addition, the intervention group will receive LCBE 500 mg (2 capsules) orally three times daily for 28 days. Follow-up visits are scheduled at baseline, day 5, day 14, and day 28, with serial assessments of TG, lipid profile, inflammatory cytokines, glucose metabolism, gut microbiota (16S rRNA sequencing), intestinal barrier biomarkers (D-lactate, endotoxin, DAO, zonulin), clinical symptoms, severity scores, and quality of life (EQ-5D-5L).
Statistical Analysis:
Analyses will follow the intention-to-treat principle, with per-protocol analysis as sensitivity analysis. Continuous variables will be compared using t-tests or Mann-Whitney U tests; categorical variables will be analyzed using chi-square or Fisher's exact tests. Microbiome diversity will be assessed using Shannon index, PERMANOVA, and LEfSe analysis. An independent Data Safety Monitoring Board will conduct one interim analysis when 50% enrollment is reached.
Ethical Considerations:
The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all participants. The trial is approved by the Institutional Review Board of Zhongshan Hospital, Xiamen University
Studietype
Intervensjonell
Registrering (Antatt)
180
Fase
- Fase 4
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Xu hongzhi PhD
- Telefonnummer: 86-0592-2292232
- E-post: xuhongzhi@xmu.edu.cn
Studer Kontakt Backup
- Navn: Liu Yunpeng PhD
- Telefonnummer: 86-0592-2292232
- E-post: liuyunpeng-84@163.com
Studiesteder
-
-
Fujian
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Xiamen, Fujian, Kina, 361004
- Rekruttering
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University
-
Ta kontakt med:
- Xu hongzhi PhD
- Telefonnummer: 86-0592-2292232
- E-post: xuhongzhi@xmu.edu.cn
-
Ta kontakt med:
- Liu Yunpeng PhD
- Telefonnummer: 86-0592-2292232
- E-post: liuyunpeng-84@163.com
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Standard Care combined LCBE
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.
|
LCBE 500 mg (2 capsules) orally three times daily for 28 ± 2 days, initiated within 24 hours after confirmation of eligibility.
Andre navn:
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.
|
|
Aktiv komparator: Standard Care Only
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.
|
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.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Mean Concentration of Serum Triglycerides (TG) in mmol/L at 5 ± 2 days.
Tidsramme: 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).
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Baseline through Day 5 (±2 days)
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Serum Concentration of C-Reactive Protein (CRP) at Day 5 (±2 days)
Tidsramme: 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.
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Baseline through Day 5 (±2 days)
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Serum Concentration of Interleukin-6 (IL-6) at Day 5 (±2 days)
Tidsramme: Baseline through Day 5 (±2 days)
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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.
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Baseline through Day 5 (±2 days)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Mean Concentration of Serum Triglycerides (TG) in mmol/L at 14 ± 2 days
Tidsramme: Baseline through Day 14 (±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 14 ± 2 days after randomization.
Values are presented as the mean (standard deviation, SD).
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Baseline through Day 14 (±2 days)
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Mean Concentration of Serum Triglycerides (TG) in mmol/L at 28 ± 2 days
Tidsramme: Baseline through Day 28 (±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 28 ± 2 days after randomization.
Values are presented as the mean (standard deviation, SD).
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Baseline through Day 28 (±2 days)
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Serum Concentration of C-Reactive Protein (CRP) at Day 14 (±2 days)
Tidsramme: Baseline through Day 14 (±2 days)
|
Fasting venous blood samples will be collected at the Day 14 (±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 14 (±2 days)
|
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Serum Concentration of C-Reactive Protein (CRP) at Day 28 (±2 days)
Tidsramme: Baseline through Day 28 (±2 days)
|
Fasting venous blood samples will be collected at the Day 28 (±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.
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Baseline through Day 28 (±2 days)
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Percentage of Participants Achieving Serum Triglyceride (TG) Normalization (<1.7 mmol/L) at Day 5 (±2 days)
Tidsramme: Baseline through Day 5 (±2 days)
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Serum TG levels will be measured from fasting blood samples collected at the Day 5 (±2 days) visit.
Normalization is defined as a TG level <1.7 mmol/L.
The outcome is the percentage of participants meeting this criterion at this specific timepoint.
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Baseline through Day 5 (±2 days)
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Percentage of Participants Achieving Serum Triglyceride (TG) Normalization (<1.7 mmol/L) at Day 14 (±2 days)
Tidsramme: Baseline through Day 14 (±2 days)
|
Serum TG levels will be measured from fasting blood samples collected at the Day 14 (±2 days) visit.
Normalization is defined as a TG level <1.7 mmol/L.
The outcome is the percentage of participants meeting this criterion at this specific timepoint.
|
Baseline through Day 14 (±2 days)
|
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Percentage of Participants Achieving Serum Triglyceride (TG) Normalization (<1.7 mmol/L) at Day 28 (±2 days)
Tidsramme: Baseline through Day 28 (±2 days)
|
Serum TG levels will be measured from fasting blood samples collected at the Day 28 (±2 days) visit.
Normalization is defined as a TG level <1.7 mmol/L.
The outcome is the percentage of participants meeting this criterion at this specific timepoint.
|
Baseline through Day 28 (±2 days)
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Percentage Change from Baseline in Serum Triglyceride (TG) Concentration at Day 5 (±2 days)
Tidsramme: Baseline through Day 5 (±2 days)
|
The percentage change will be calculated using the formula: [(TG at Day 5) - (TG at Baseline)] / (TG at Baseline) × 100%.
Fasting blood samples will be collected at both timepoints.
A negative value indicates a reduction in TG levels.
Data will be presented as Mean (Standard Deviation, SD).
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Baseline through Day 5 (±2 days)
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Percentage Change from Baseline in Serum Triglyceride (TG) Concentration at Day 14 (±2 days)
Tidsramme: Baseline through Day 14 (±2 days)
|
The percentage change will be calculated using the formula: [(TG at Day 14) - (TG at Baseline)] / (TG at Baseline) × 100%.
A negative value indicates a reduction in TG levels.
Data will be presented as Mean (SD).
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Baseline through Day 14 (±2 days)
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Percentage Change from Baseline in Serum Triglyceride (TG) Concentration at Day 28 (±2 days)
Tidsramme: Baseline through Day 28 (±2 days)
|
The percentage change will be calculated using the formula: [(TG at Day 28) - (TG at Baseline)] / (TG at Baseline) × 100%.
A negative value indicates a reduction in TG levels.
Data will be presented as Mean (SD).
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Baseline through Day 28 (±2 days)
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Percentage Change from Baseline in Serum C-Reactive Protein (CRP) at Day 5 (±2 days)
Tidsramme: Baseline through Day 5 (±2 days)
|
The percentage change will be calculated as: [(CRP at Day 5) - (CRP at Baseline)] / (CRP at Baseline) × 100%.
Serum CRP will be measured using a high-sensitivity immunoturbidimetric assay.
A negative value indicates a reduction in systemic inflammation.
Data will be presented as Median (Interquartile Range, IQR).
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Baseline through Day 5 (±2 days)
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Percentage Change from Baseline in Serum C-Reactive Protein (CRP) at Day 14 (±2 days)
Tidsramme: Baseline through Day 14 (±2 days)
|
The percentage change will be calculated as: [(CRP at Day 14) - (CRP at Baseline)] / (CRP at Baseline) × 100%.
A negative value indicates a reduction in systemic inflammation.
Data will be presented as Median (IQR).
|
Baseline through Day 14 (±2 days)
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Percentage Change from Baseline in Serum C-Reactive Protein (CRP) at Day 28 (±2 days)
Tidsramme: Baseline through Day 28 (±2 days)
|
The percentage change will be calculated as: [(CRP at Day 28) - (CRP at Baseline)] / (CRP at Baseline) × 100%.
A negative value indicates a reduction in systemic inflammation.
Data will be presented as Median (IQR).
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Baseline through Day 28 (±2 days)
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Percentage Change from Baseline in Serum Interleukin-6 (IL-6) at Day 5 (±2 days)
Tidsramme: Baseline through Day 5 (±2 days)
|
The percentage change will be calculated as: [(IL-6 at Day 5) - (IL-6 at Baseline)] / (IL-6 at Baseline) × 100%.
Serum IL-6 will be measured using a chemiluminescence immunoassay or ELISA.
Data will be presented as Median (Interquartile Range, IQR).
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Baseline through Day 5 (±2 days)
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Change from Baseline in Gut Microbiota Alpha and Beta Diversity Indices Assessed by 16S rRNA Sequencing
Tidsramme: Baseline through Day 28 (±2 days)
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Fecal samples will be collected at Baseline, Day 5, Day 14, and Day 28.
Gut microbiota composition will be profiled using 16S rRNA gene sequencing (V3-V4 regions).
Alpha diversity (including Shannon, Simpson, Chao1, and Observed OTUs indices) and beta diversity (using Bray-Curtis dissimilarity and Weighted UniFrac distances) will be calculated via the QIIME2 pipeline.
Changes from baseline at each timepoint will be evaluated.
LEfSe analysis will identify differentially abundant taxa (LDA score >2.0, P<0.05).
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Baseline through Day 28 (±2 days)
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Change from Baseline in Serum Intestinal Barrier Biomarkers (D-lactate, Endotoxin, DAO, Zonulin)
Tidsramme: Baseline through Day 28 (±2 days)
|
Fasting venous blood samples will be collected at Baseline, Day 5 (±2 days), Day 14 (±2 days), and Day 28 (±2 days).
Serum will be separated and stored at -80°C until batch analysis.
Biomarker concentrations will be measured using commercially available ELISA kits: D-lactate by enzymatic spectrophotometry, endotoxin by the chromogenic limulus amebocyte lysate (LAL) assay, diamine oxidase (DAO) by ELISA, and zonulin by ELISA.
Changes from baseline at each timepoint will be calculated.
Data will be presented as Mean (Standard Deviation, SD) or Median (Interquartile Range, IQR) as appropriate.
These biomarkers will be correlated with gut microbiota profiles and clinical outcomes.
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Baseline through Day 28 (±2 days)
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Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Time to Abdominal Pain Relief
Tidsramme: From randomization up to Day 28 (±2 days)
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Abdominal pain intensity will be assessed every 2 hours by nursing staff using a Visual Analogue Scale (VAS; 0-100 mm) blinded to group allocation.
Abdominal pain relief is defined as the time from randomization to the first instance when the VAS score decreases to ≤30 (mild pain or less) and remains at or below this level for at least 12 consecutive hours without rescue analgesia.
Patients requiring surgical intervention, discharged, or experiencing a serious adverse event prior to achieving relief will be censored at the time of that event.
Data will be presented as Median Time (Interquartile Range, IQR)
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From randomization up to Day 28 (±2 days)
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Time to Successful Oral Feeding
Tidsramme: From randomization up to Day 28 (±2 days)
|
Defined as the time from randomization to the first instance when the participant tolerates a regular or semi-solid diet without experiencing recurrence of moderate to severe abdominal pain (Visual Analogue Scale, VAS >30) or other gastrointestinal symptoms (e.g., nausea, vomiting, abdominal distension) for at least 24 consecutive hours.
Dietary tolerance will be assessed daily by the attending physician or study nurse blinded to group allocation.
Patients requiring surgical intervention, discharged, or experiencing a serious adverse event prior to achieving successful oral feeding will be censored at the time of that event.
Data will be presented as Median Time (Interquartile Range, IQR).
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From randomization up to Day 28 (±2 days)
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Length of Hospital Stay
Tidsramme: From admission to discharge, up to Day 28 (±2 days)
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Defined as the number of calendar days from the date of hospital admission to the date of discharge (discharge criteria: absence of abdominal pain, tolerance of solid food, and normalization of inflammatory markers).
For participants transferred to another facility (e.g., ICU) or those who die during hospitalization, the length of stay will be censored at the date of the last known status.
Data will be presented as Median (Interquartile Range, IQR) in days.
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From admission to discharge, up to Day 28 (±2 days)
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Total Hospitalization Cost
Tidsramme: From admission to discharge, up to Day 28 (±2 days)
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Total direct medical costs incurred from admission to discharge will be extracted from the hospital's electronic billing system.
Costs include expenses related to medications (including study drugs), laboratory tests, imaging examinations, bed occupancy, surgical procedures, and medical consumables.
All costs will be converted to Chinese Yuan (CNY) and adjusted for inflation if necessary.
Costs for participants transferred to other facilities (e.g., ICU) or those who die during hospitalization will be calculated up to the date of the last known status.
Data will be presented as Median (Interquartile Range, IQR) due to the typically skewed distribution of cost data.
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From admission to discharge, up to Day 28 (±2 days)
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Rate of Intensive Care Unit (ICU) Admission During Hospitalization
Tidsramme: From admission to discharge, up to Day 28 (±2 days)
|
Defined as the proportion of participants who require transfer to or direct admission into an intensive care unit (ICU) at any point during the index hospitalization.
This includes transfers for respiratory failure, hemodynamic instability, or organ support (e.g., mechanical ventilation, continuous renal replacement therapy).
The outcome is assessed via daily review of medical records and nursing flow sheets.
Data will be presented as a percentage with a 95% Confidence Interval (CI).
Participants who die prior to a potential ICU transfer will be counted as having met the endpoint.
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From admission to discharge, up to Day 28 (±2 days)
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Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Tidsramme: From randomization to end of treatment (Day 28 ± 2 days)
|
Adverse Events (AEs) and Serious Adverse Events (SAEs) will be monitored continuously from the time of informed consent until the end of the follow-up period (Day 28).
AEs will be classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 6.0.
The severity (Grade 1-5) and relationship to the study intervention (certain, probable/likely, possible, unlikely, unrelated) will be assessed by the investigator.
SAEs will be reported to the Institutional Review Board and the sponsor within 24 hours.
The incidence will be calculated as the number of participants experiencing at least one event divided by the total number of participants in each arm.
Data will be presented as the number of participants (n) and percentage (%) with corresponding 95% Confidence Intervals.
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From randomization to end of treatment (Day 28 ± 2 days)
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Quality of Life Assessed by EuroQol 5-Dimension 5-Level (EQ-5D-5L) Utility Score
Tidsramme: Baseline through Day 28 (±2 days)
|
Health-related quality of life (HRQoL) will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, a standardized generic instrument covering 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Participants will complete the questionnaire independently at Baseline, Day 5 (±2 days), Day 14 (±2 days), and Day 28 (±2 days) under the guidance of study staff blinded to group allocation.
Utility scores will be derived using the Chinese adult population preference-based scoring algorithm, with a theoretical range of -0.391 (worst possible health state, equivalent to coma/death) to 1.0 (full health).
Higher scores indicate better HRQoL; lower scores reflect greater impairment in daily functioning and well-being.
Data will be presented as Mean (Standard Deviation, SD), with sensitivity analyses using Median (Interquartile Range, IQR) if data deviate from normality.
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Baseline through Day 28 (±2 days)
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Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.
- Elshaghabee FMF, Rokana N, Gulhane RD, Sharma C, Panwar H. Bacillus As Potential Probiotics: Status, Concerns, and Future Perspectives. Front Microbiol. 2017 Aug 10;8:1490. doi: 10.3389/fmicb.2017.01490. eCollection 2017.
- Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE. APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med. 1981 Aug;9(8):591-7. doi: 10.1097/00003246-198108000-00008.
- Tenner S, Vege SS, Sheth SG, Sauer B, Yang A, Conwell DL, Yadlapati RH, Gardner TB. American College of Gastroenterology Guidelines: Management of Acute Pancreatitis. Am J Gastroenterol. 2024 Mar 1;119(3):419-437. doi: 10.14309/ajg.0000000000002645. Epub 2023 Nov 7.
- Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974 Jul;139(1):69-81. No abstract available.
- Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008 Dec;57(12):1698-703. doi: 10.1136/gut.2008.152702. Epub 2008 Jun 2.
- Mortele KJ, Wiesner W, Intriere L, Shankar S, Zou KH, Kalantari BN, Perez A, vanSonnenberg E, Ros PR, Banks PA, Silverman SG. A modified CT severity index for evaluating acute pancreatitis: improved correlation with patient outcome. AJR Am J Roentgenol. 2004 Nov;183(5):1261-5. doi: 10.2214/ajr.183.5.1831261.
- Kee Jang D, Kyu Lee J, Yung Jung C, Ho Kim K, Ra Kang H, Sun Lee Y, Hwa Yoon J, Ro Joo K, Kyu Chae M, Hyeon Baek Y, Seo BK, Hyub Lee S, Lim C. Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial. J Integr Med. 2023 Nov;21(6):537-542. doi: 10.1016/j.joim.2023.10.004. Epub 2023 Nov 2.
- Pi X, Teng W, Fei D, Zhao G, Liu W. Effects of Live Combined Bacillus subtilis and Enterococcus faecium on Gut Microbiota Composition in C57BL/6 Mice and in Humans. Front Cell Infect Microbiol. 2022 Feb 10;12:821662. doi: 10.3389/fcimb.2022.821662. eCollection 2022.
- Wan YD, Zhu RX, Bian ZZ, Sun TW. Effect of probiotics on length of hospitalization in mild acute pancreatitis: A randomized, double-blind, placebo-controlled trial. World J Gastroenterol. 2021 Jan 14;27(2):224-232. doi: 10.3748/wjg.v27.i2.224.
- Guo L, Meng M, Wei Y, Lin F, Jiang Y, Cui X, Wang G, Wang C, Guo X. Protective Effects of Live Combined B. subtilis and E. faecium in Polymicrobial Sepsis Through Modulating Activation and Transformation of Macrophages and Mast Cells. Front Pharmacol. 2019 Jan 21;9:1506. doi: 10.3389/fphar.2018.01506. eCollection 2018.
- Wu Y, Wu H, Yi H. Efficacy of interventions with live combined Bacillus subtilis and Enterococcus faecium enteric-coated capsules in metabolic associated fatty liver disease patients: a meta-analysis of randomized controlled trials. Front Pharmacol. 2025 May 27;16:1610426. doi: 10.3389/fphar.2025.1610426. eCollection 2025.
- Jiang J, Xiong J, Ni J, Chen C, Wang K. Live Combined B. subtilis and E. faecium Alleviate Liver Inflammation, Improve Intestinal Barrier Function, and Modulate Gut Microbiota in Mice with Non-Alcoholic Fatty Liver Disease. Med Sci Monit. 2021 Sep 5;27:e931143. doi: 10.12659/MSM.931143.
- Huang J, Huang J, Yin T, Lv H, Zhang P, Li H. Enterococcus faecium R0026 Combined with Bacillus subtilis R0179 Prevent Obesity-Associated Hyperlipidemia and Modulate Gut Microbiota in C57BL/6 Mice. J Microbiol Biotechnol. 2021 Feb 28;31(2):181-188. doi: 10.4014/jmb.2009.09005.
- Mo SJ, Lee K, Hong HJ, Hong DK, Jung SH, Park SD, Shim JJ, Lee JL. Effects of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 on Overweight and the Gut Microbiota in Humans: Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Nutrients. 2022 Jun 15;14(12):2484. doi: 10.3390/nu14122484.
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Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
18. januar 2026
Primær fullføring (Antatt)
18. januar 2028
Studiet fullført (Antatt)
18. februar 2029
Datoer for studieregistrering
Først innsendt
3. juli 2026
Først innsendt som oppfylte QC-kriteriene
18. juli 2026
Først lagt ut (Faktiske)
22. juli 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
22. juli 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
18. juli 2026
Sist bekreftet
1. juli 2026
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Metabolske sykdommer
- Sykdommer i fordøyelsessystemet
- Pankreassykdommer
- Dyslipidemier
- Lipidmetabolismeforstyrrelser
- Ernæringsmessige og metabolske sykdommer
- Pankreatitt
- Hyperlipidemier
- Health Services Administration
- Helsevesenets kvalitet, tilgang og evaluering
- Kvalitet på helsehjelpen
- Kvalitetsindikatorer, helsehjelp
- Standard for omsorg
Andre studie-ID-numre
- XUZH20260005
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
JA
IPD-planbeskrivelse
Individual participant data (IPD) underlying the primary and secondary outcomes will be shared.
This includes de-identified baseline characteristics, clinical measurements (e.g., serum triglyceride levels, lipid profiles, CRP, IL-6, HOMA-IR, TyG), intestinal barrier biomarkers, 16S rRNA gene sequencing data (processed OTU/ASV tables), and safety data (adverse events).
The study protocol and statistical analysis plan will also be available.
Data will be accessible beginning 12 months after publication and ending 36 months after publication.
Researchers with scientifically valid proposals approved by an independent review committee will be granted access upon signing a data sharing agreement.
IPD-delingstidsramme
Beginning 12 months after publication, ending 36 months after publication.
Tilgangskriterier for IPD-deling
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.
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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