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

NCT06199752 | Completed Phase 4 FDA Drug

• 1 other identifier: Synbiotics in cancer
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (3)

Placebo

ACTIVE COMPARATOR

Placebo consisted of identical capsules of powdered glucose polymer

Dietary Supplement: probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA

Synbiotics group

PLACEBO COMPARATOR

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

Probiotics group

PLACEBO COMPARATOR

probiotic agent 25 Billion CFU (Nowfoods, USA)

Dietary Supplement: probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA

Interventions

probiotic agent 25 Billion CFU (Nowfoods, USA) , ). Inulin capsules 1000mg Herbamama USA DIETARY_SUPPLEMENT

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; Probiotics group; Synbiotics group

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Theodor Bilharz Research Institute: lead

Study Sites (1)

Sara Maher

Cairo, 12411, Egypt

Location

Related Publications (2)

• 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.

  PMID: 34959977 BACKGROUND

• Maher S, Elmeligy HA, Aboushousha T, Helal NS, Ossama Y, Rady M, Hassan AMA, Kamel M. Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study. Cancer Immunol Immunother. 2024 Apr 25;73(6):109. doi: 10.1007/s00262-024-03686-6.

  PMID: 38662232 DERIVED

MeSH Terms

Interventions

Inulin

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides

Study Officials

• Sara Maher

  Theodor Bilharz Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: January 10, 2024
• Study Start: December 12, 2021
• Primary Completion: April 20, 2023
• Study Completion: September 10, 2023
• Last Updated: January 10, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)