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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Dietary supplement: probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 12411
    • Sara Maher

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo; Placebo consisted of identical capsules of powdered glucose polymer	Dietary supplement: probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA; probiotic agent 25 Billion CFU (Nowfoods, USA), composed of ten strains of bacteria (Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantaLactobacillus paracasei, Bifidobacterium breve, Streotococcus thermophiles, Lactobacillus salivarius, and Bifidobacterium longum),
Placebo Comparator: Synbiotics group; probiotic agent 25 Billion CFU (Nowfoods, USA), + Inulin capsules 1000mg two capsules once daily. Herbamama USA	Dietary supplement: probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA; probiotic agent 25 Billion CFU (Nowfoods, USA), composed of ten strains of bacteria (Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantaLactobacillus paracasei, Bifidobacterium breve, Streotococcus thermophiles, Lactobacillus salivarius, and Bifidobacterium longum),
Placebo Comparator: Probiotics group; probiotic agent 25 Billion CFU (Nowfoods, USA)	Dietary supplement: probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA; probiotic agent 25 Billion CFU (Nowfoods, USA), composed of ten strains of bacteria (Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantaLactobacillus paracasei, Bifidobacterium breve, Streotococcus thermophiles, Lactobacillus salivarius, and Bifidobacterium longum),

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunohistochemistry testing for immune cells infiltration and interferon-gamma expression	Change in the percentage of infiltrating CD8T cells in the tumor tissue as well as the interferon-gamma in synbiotics group	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
Inflammatory cytokines level	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	10 months after collection of all blood samples from included subjects
Post-operative -non-infectious complications- improvement	Testing the percentage of subjects having Anastomotic Leakage, Diarrhea, Abdominal distension	1-4 weeks post operative
Post-operative -infectious complications improvement	Testing the percentage of subjects having Bacteremia, Wound infection, Pneumonia, Urinary tract infection	1-4 weeks post operative
Post-operative improvement days	Number of days for first stool, stay in the hospital and return to usual activity	first day post operative till 20 days
Statistical analysis of the results	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.	11 months from the beginning of the study

Collaborators and Investigators

• Sponsor: Theodor Bilharz Research Institute
• Investigators: Principal Investigator: Sara Maher, Theodor Bilharz Research Institute

Publications and helpful links

General Publications

• Sobocki BK, Kazmierczak-Siedlecka K, Folwarski M, Hawrylkowicz V, Makarewicz W, Stachowska E. Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations. Nutrients. 2021 Dec 10;13(12):4425. doi: 10.3390/nu13124425.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2021
• Primary Completion (Actual): April 20, 2023
• Study Completion (Actual): September 10, 2023

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: Synbiotics in cancer

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