The Effects of Probiotics on Intestinal Permeability in Gastrointestinal Cancer Patients in Chemotherapy

NCT ID: NCT03704727

Last Updated: 2019-04-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2019-02-01

Brief Summary

The aim of this study is to test the hypothesis that adjuvant administration of probiotics in cancer patients undergoing chemotherapy can reduce a chemo-induced increased intestinal permeability. Furthermore, we hypothesize that the use of probiotics may reduce the occurrence of gastrointestinal side effects such as diarrhea, abdominal pains, bacterial translocation and infections following chemotherapy.

Detailed Description

Treatment of most cancer patients involves radiation and/or chemotherapy which often leads to gastrointestinal toxicity. Cytotoxic chemotherapy in particular often induces several intestinal abnormalities such as mucositis including destruction of intestinal villi, alterations in the gut microbiota, modulation of tight junctions, leading to an increased intestinal permeability. These toxic effects have been observed in several types of chemotherapy and different methods of administering chemotherapy.

The intestinal permeability is regulated and protected by a number factors, including a mucus layer covering the surface of the epithelium. This mucus layer is partly regulated by intestinal bacteria. Therefore it is hypothesized that chemoinduced changes in the intestinal microbiota may possibly affect intestinal permeability. Changes in the intestinal microbiota are seen after only one or a few cycles of chemotherapy treatment in different types of cancers, and could possibly be a contributing factor in the development of mucositis.

It is possible that probiotics may interfere with the ability of pathogenic bacteria to bind to the surface of the intestinal epithelial lining. In vitro studies have shown that probiotics may reduce a post-infective (Escherichia coli) increased intestinal permeability, or increased permeability due to incubation with pro-inflammatory cytokines. VSL#3 is a probiotic formula containing a mixture of 9x10^10 CFU/g Lactobacilli strains (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, and Lactobacillus bulgaricus), 8x10^10 CFU/g Bifidum strains (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis) and 20x10^10 CFU/g Streptococcus thermophilus. In vitro and ex vivo studies have suggested that the probiotic bacteria found in VSL#3 may have a reducing effect on intestinal permeability as well as a positive modulating effect on tight junction protein expression. Escherichia coli Nissle 1917 is another bacterial strain that has been shown to be able to mediate the modulation of tight junction proteins and thus intestinal permeability. The precise mechanisms behind the effects of probiotics on intestinal epithelial permeability are not yet clear, but some mechanisms have been proposed, including a reduction in bacterial secretion of proinflammatory cytokines as well as other secreted products from probiotic microbial metabolism.

It is not known whether all probiotic strains exert a similar effect on intestinal permeability, as only very limited clinical research has addressed this relation. However, it is very likely that the specific choice of probiotic bacterial species may play a crucial role. We are only familiar with one clinical trial examining the effect of probiotics on intestinal permeability in adults with cancer undergoing treatment in the form of colectomy, but no adjuvant chemotherapy. Probiotics in the form of Lactobacillus plantarum, Lactobacillus acidophilus and Bifidobacterium longum was administered perioperative and postoperative to patients undergoing colectomy, and the study showed that probiotics improved the integrity of the small intestinal mucosal barrier, induced modulation of the intestinal microbiome as well as a reduction in the postoperative rate of infections.The same researchers also measured serum zonulin in the same subjects, and found that the treatment with probiotics also reduced the concentration of postoperative serum zonulin, and thus inhibited the same increase in intestinal permeability as was the case in the control group.

Conditions

Intestinal Permeability; Gastrointestinal Irritation; Mucositis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

probiotic treatment

Probiotic: VSL#3 is a probiotic formula containing a mixture of 9x10\^10 CFU/g Lactobacilli strains (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, and Lactobacillus bulgaricus), 8x10\^10 CFU/g Bifidum strains (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis) and 20x10\^10 CFU/g Streptococcus thermophilus. Administred orally

Group Type: EXPERIMENTAL

Probiotic

Intervention Type: DIETARY_SUPPLEMENT

Probiotics (beneficial microorganisms) VSL#3 is a probiotic formula containing a mixture of 9x10\^10 CFU/g Lactobacilli strains (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, and Lactobacillus bulgaricus), 8x10\^10 CFU/g Bifidum strains (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis) and 20x10\^10 CFU/g Streptococcus thermophilus

Interventions

Probiotic

Probiotics (beneficial microorganisms) VSL#3 is a probiotic formula containing a mixture of 9x10\^10 CFU/g Lactobacilli strains (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, and Lactobacillus bulgaricus), 8x10\^10 CFU/g Bifidum strains (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis) and 20x10\^10 CFU/g Streptococcus thermophilus

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• GI cancer (all types) patients undergoing chemotherapy in oncologic department at Rigshospitalet in Copenhagen
• Age >18 years
• Patients with at least three planned chemo therapy sessions left

Exclusion Criteria

• Pregnant
• Patients who don't speak, write or understand Danish
• Known inflammatory bowel diseases or malabsorption
• Chronic kidney disease (2 x upper limit plasma creatinine)
• Neutropenia (< 1.5 x 109/L neutrophilic granulocytes in peripheral blood)
• Use of antibiotics
• Use of lactulose (laxative) and not able to discontinue three days prior to urin collection (lactulose/mannitol test)
• Use of probiotics

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actial Farmaceutica S.r.l.

INDUSTRY

Sponsor Role: collaborator

Nutricia, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Jens Rikardt Andersen

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jens R Andersen, MD,MPA

Role: PRINCIPAL_INVESTIGATOR

University of Copenhagen

Locations

Departmen of Oncology, Rigshospital

Copenhagen, , Denmark

Countries

Denmark

Other Identifiers

H-18010425

Identifier Type: -

Identifier Source: org_study_id