Therapeutic Effect of Bifidobacterium Longum in Patients with Acute Pancreatitis: a Randomized, Double-Blind, Placebo-Controlled Trial

The purpose of this clinical trial is to investigate the impact of Bifidobacterium longum(BL) on the clinical prognosis of patients with acute pancreatitis(AP), to analyze the correlation between BL and intestinal barrier function, as well as the gut microbiota, and to observe adverse reactions and risks in patients with AP after the use of BL.

Participants will be randomly assigned to two groups: the intervention group and the control group. They will receive:

• Intervention group: Standard clinical treatment + BL capsules (10^10 CFU), twice a day, for a total of 14 days;
• Control group: Standard clinical treatment + placebo capsules, for a total of 14 days.

A total of 60 patients will be included in this study.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Pancreatitis
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Bifidobacterium longum; Combination product: Standard clinical treatment

Detailed Description

Rationale:The impairment of the intestinal mucosal barrier in patients with acute pancreatitis (AP) plays a crucial role in the progression to severe AP(SAP). Our previous research found that the early gut microbiota structure of AP patients is significantly different from that of healthy individuals, characterized by a marked increase in the relative abundance of conditional pathogens such as Escherichia coli and Shigella, while beneficial bacteria that produce short-chain fatty acids, such as Bifidobacterium, are significantly reduced, especially in patients with SAP. Bifidobacterium longum (BL), a well-known probiotic, has been used to treat a variety of diseases. In our previous animal experiments, we found that BL could alleviate pancreatic damage and inflammatory responses in AP mice and regulate the balance of the gut microbiota. Based on these findings, this study aims to assess the impact of BL on the clinical prognosis of AP patients through a randomized controlled trial, in order to provide a scientific basis for the application of BL in the treatment of AP and to further explore its potential clinical value.

Objective: The purpose of this clinical trial is to investigate the impact of BL on the clinical prognosis of patients with AP, to analyze the correlation between BL and intestinal barrier function, as well as the gut microbiota, and to observe adverse reactions and risks in patients with AP after the use of BL.

Study design: Single-center, randomized, double-blind, placebo-controlled study.

Study population:60 adult patients with acute pancreatitis. Intervention: The intervention group receives standard clinical treatment plus BL capsules (10^10 CFU), twice a day, for a total of 14 days; the control group receives standard clinical treatment plus placebo capsules, for a total of 14 days.

Main study parameters/endpoints: The primary endpoint is the number of days without SIRS within 14 days; the secondary endpoints include infectious complications (including fungal infections), parameters related to systemic inflammatory response, intestinal barrier function and gut microbiota composition, indicators related to recovery of intestinal function, antibiotic use, laboratory-related indicators, and clinical outcomes.

Safety: Throughout the study (or afterwards), treatment-emergent adverse events (TEAEs) were recorded, including gastrointestinal adverse reactions (abdominal pain, nausea, vomiting, bloating, or diarrhea) and allergic reactions, and adverse events that led to discontinuation of the study drug were documented.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: yin zhu, PhD; Phone Number: +8613970847464; Email: ndyfy01977@ncu.edu.cn

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
      • Contact: Cong He, PhD; Phone Number: +8613807032823; Email: hecong.1987@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-75 year;
2. The diagnosis of acute pancreatitis according to the revised Atlanta classification;
3. The onset time of acute pancreatitis is within 48 hours;
4. APACHE II score of ≥8, or C-reactive protein > 150 mg/L, or SIRS score of ≥3;
5. Signed the informed consent.

Exclusion Criteria:

1. Within 48 hours of onset, there is multi-organ failure;
2. Use of probiotics within the last month;
3. Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP);
4. Intra-operative diagnosis;
5. Infection/sepsis caused by a second disease;
6. Malignancy;
7. Immunocompromised patients;
8. Pregnancy and/or lactation;
9. Allergy to Bifidobacterium longum.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Placebo capsules twice daily for 14 days	Dietary supplement: Placebo; Placebo; Combination product: Standard clinical treatment; Fasting, gastrointestinal decompression, rehydration, inhibition of pancreatic fluid and pancreatic enzyme secretion, improvement of microcirculation, and support of organ function if organ dysfunction occurs at a later stage (mechanical ventilation, continuous renal replacement therapy, and the use of vasoactive drugs).
Experimental: Intervention group; Bifidobacterium longum capsules (10^10 CFU) twice daily for 14 days	Dietary supplement: Bifidobacterium longum; Bifidobacterium longum; Combination product: Standard clinical treatment; Fasting, gastrointestinal decompression, rehydration, inhibition of pancreatic fluid and pancreatic enzyme secretion, improvement of microcirculation, and support of organ function if organ dysfunction occurs at a later stage (mechanical ventilation, continuous renal replacement therapy, and the use of vasoactive drugs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of days without SIRS within 14 days	Patients were randomized into the study group and remained free of SIRS up to 14 days after enrollment, with the total number of SIRS-free days counted	From randomization to 14 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Occurence of death	During the whole study period including follow-up of 90 days
(New onset) transient/persistant (multiple) organ failure	The occurence of (new onset) transient/persistant (multiple) organ failure	During the whole study period including follow-up of 90 days
Disease severity according to the revised Atlanta Classification	Disease severity according to the revised Atlanta Classification	During the whole study period including follow-up of 90 days
The need (and number of) for surgical, endoscopic or radiologic interventions	The need (and number of) for surgical, endoscopic or radiologic interventions	During the whole study period including follow-up of 90 days
Readmissions	The occurrence and number of readmissions	During the whole study period including follow-up of 90 days
Infectious complications	The occurence of infected pancreatic necrosis, bacteremia, pneumonia, urosepsis, and/or infected ascites，including fungal infections	During the whole study period including follow-up of 90 days
Intestinal barrier function	Plasma D-lactate(D-lac）	Through study completion, an average of 1 year
Intestinal barrier function	Diamine oxidase activity(DAO)	Through study completion, an average of 1 year
Intestinal barrier function	Plasma endotoxin levels	Through study completion, an average of 1 year
Gut microbiota composition	Fecal samples were collected from patients prior to the start of treatment, as well as on days 3, 7, and 14 after treatment. Subsequently, DNA was extracted from the feces, and the DNA was fragmented by Covaris M220 to screen for fragments of approximately 350 bp to be constructed into paired-end (Paired-End) DNA libraries. Next, libraries were constructed using NEXTFLEX Rapid DNA-Seq. Finally, these libraries were subjected to macro-genomic sequencing for in-depth analysis of microbial community structure and function in the samples.	Baseline , 3 days，7 days and 14 days of treatment
Systemic inflammatory response parameters (SIRS)	The incidence of persistent SIRS (lasting ≥48 hours)	Through study completion, an average of 1 year
Systemic inflammatory response parameters (SIRS)	Trends in SIRS score changes	Through study completion, an average of 1 year
Systemic inflammatory response parameters (SIRS)	Trends in CRP level changes	Through study completion, an average of 1 year
Gut function recovery-related indicators	Improvement in abdominal signs	Through study completion, an average of 1 year
Antibiotic usage	The number of days of antibiotic use	Through study completion, an average of 1 year
Length of hospital and/or ICU stay	Measured in days	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Nanchang University
• Investigators: Principal Investigator: Cong He, PhD, The First Affiliated Hospital of Nanchang University

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 2, 2024
• First Submitted That Met QC Criteria: October 10, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Probiotics; acute pancreatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis
• Other Study ID Numbers: Bifidobacterium Longum

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No