Synergistic Immunomodulatory Effect of Synbiotics Pre and Postoperative Resection of Pancreatic Ductal Adenocarcinoma

Phase 4

Completed

• Conditions: Pancreatic Ductal Adenocarcinoma
• Interventions: Dietary Supplement: probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA

• Registration Number: NCT06199752
• Lead Sponsor: Theodor Bilharz Research Institute

Brief Summary

The goal of this interventional study was to evaluate the synergistic effect of symbiotics (a combination of probiotics and prebiotics) compared to probiotics alone in terms of their impact on anti-tumor immunomodulation in patients with pancreatic ductal adenocarcinoma (PDAC). The study also aimed to assess the effects of these interventions on postoperative complications and outcomes. In the study, a probiotic agent (Nowfoods, USA), containing ten strains of bacteria with a total dosage of 25 billion colony-forming units (CFU) was administered. This probiotic regimen involved taking two capsules once daily, starting two weeks before the surgery and continuing for one month after the surgery. For the synbiotic group, in addition to the probiotic agent, two capsules per day of inulin supplement (HERBAMAMA, USA) were also taken.

The study included three groups: the synbiotics group, the probiotics group, and the placebo group. The researchers compared the pathological status of immune cell infiltration (specifically CD8 cells) and interferon-gamma expression, as well as the levels of interleukins 10, 6, and 10 in the participants' serum. Four blood samples were collected from each participant: one taken 14 days before the surgery, one on the surgery date, one two weeks after the surgery, and one 30 days after the surgery.

The main research question addressed by the study was whether there was a significant difference in the immunomodulatory effect and postoperative complications between the synbiotics group and the probiotics group. The placebo group likely served as a control to compare the effects of the interventions against no intervention.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-12-12
• Primary Completion: 2023-04-20
• Study Completion: 2023-09-10
• Study First Submitted: 2023-11-29
• Status Verified: 2023-12
• Study First Submitted QC: 2023-12-27
• Last Update Submitted: 2023-12-27
• Study First Posted: 2024-01-10
• Last Update Posted: 2024-01-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Patients with primary PDAC with complete pathological and follow-up data
• Patients without long-distance metastasis
• Patients without chronic diseases
• Patients without any treatments before the surgery.

Exclusion Criteria

• Patients who suffered from other tumors or other chronic diseases or accidentally died
• Lack of pathological and follow-up data.
• Patients with long-distance metastasis before the surgery.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA	Placebo consisted of identical capsules of powdered glucose polymer
Probiotics group	probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA	probiotic agent 25 Billion CFU (Nowfoods, USA)
Synbiotics group	probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA	probiotic agent 25 Billion CFU (Nowfoods, USA), + Inulin capsules 1000mg two capsules once daily. Herbamama USA

Primary Outcome Measures

Name	Time	Method
Immunohistochemistry testing for immune cells infiltration and interferon-gamma expression	IHC testing for formalin fixed paraffin embedded block for all subjects 10 months from the beginning of the study, as we collected the all samples	Change in the percentage of infiltrating CD8T cells in the tumor tissue as well as the interferon-gamma in synbiotics group
Post-operative -non-infectious complications- improvement	1-4 weeks post operative	Testing the percentage of subjects having Anastomotic Leakage, Diarrhea, Abdominal distension
Post-operative -infectious complications improvement	1-4 weeks post operative	Testing the percentage of subjects having Bacteremia, Wound infection, Pneumonia, Urinary tract infection
Inflammatory cytokines level	10 months after collection of all blood samples from included subjects	A change in the inflammatory cytokines levels (IL 10, IL6, and IL 1 β) in synbiotics-treated group with a significant difference rather the placebo and probiotics only treated groups
Post-operative improvement days	first day post operative till 20 days	Number of days for first stool, stay in the hospital and return to usual activity
Statistical analysis of the results	11 months from the beginning of the study	To assess the significance of changes in the percentage of CD8 cells in the tissue in all subjected groups as well as the expression of Interferon-gamma protein. Also, the concentration of circulating cytokines including IL B, IL6, and IL 10.; Data were analyzed using statistical software package (IBM-SPSS) version 23 software. Kolmogorov-Smirnov test showed that the raw data were normally distributed. One ANOVA was applied to study the effect of treatment on the studied parameters. Two-way ANOVA was applied to study the effect of time and treatment on the studied parameters. The least significant difference (LSD) test was used to illustrate the statistical differences among the experimental groups. Duncan's test was used to illustrate the homogeneity among the different intervals. Data is displayed as mean ± standard error of the mean.

Trial Locations

Locations (1)

Sara Maher; 🇪🇬 Cairo, Egypt