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Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Dysbiosis (EBP)

Primary Purpose

Dysbiosis

Status
Recruiting
Phase
Not Applicable
Locations
Austria
Study Type
Interventional
Intervention
Intervention
Sponsored by
Medical University of Graz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dysbiosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age >18; Signed Informed Consent; PPI intake for at least 3 months; Willing to accept use of all encoded data, including publication, and the confidential use and storage of all data for at least 15 years; Exclusion criteria Diagnosed with a gastrointestinal infection within 4 weeks prior to screening; Severe gastrointestinal disorders (e.g. inflammatory bowel diseases) Received any of the following products/medication prior to screening: systemic antibiotics, prokinetics, prebiotic supplements, probiotic supplements within 4 weeks prior to screening; Concomitant diseases or other circumstances that suggest that the patients are not eligible for participation in the study

Sites / Locations

  • Medical University GrazRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention

Arm Description

The study product contains Lactobacillus acidophilus W53, Lactobacillus acidophilus W55, Lactobacillus casei W56, Lactobacillus plantarum W1, Lactobacillus plantarum W21, Lactobacillus rhamnosus W71, and Pediococcus acidilactici W143.

Outcomes

Primary Outcome Measures

Changes in overall symptom score
Gastrointestinal quality of life index (GIQLI)

Secondary Outcome Measures

Other dimension of gastrointestinal quality of life
Gastrointestinal quality of life index (GIQLI)
Composition of the faecal metabolome
NMR metabolomics
Zonulin
measurement of faecal zonulin
Calprotectin
measurement of faecal calprotectin
Diaminooxidase
measurement of serum diaminooxidase
lipopolysaccharide binding protein
measurement of serumlipopolysaccharide binding protein
soluble CD14
measurement of serum soluble CD14
Veillonella parvula
measurement of stool Veillonella parvula gene abundance
Streptococcus salivarius
measurement of stool Streptococcus salivarius gene abundance

Full Information

First Posted
April 18, 2023
Last Updated
August 1, 2023
Sponsor
Medical University of Graz
Collaborators
CBmed Ges.m.b.H.
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1. Study Identification

Unique Protocol Identification Number
NCT05836155
Brief Title
Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Dysbiosis
Acronym
EBP
Official Title
Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Gastrointestinal Discomfort and Oralization of the Gut Microbiome: An Open-label Pilot Single-arm Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2023 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Graz
Collaborators
CBmed Ges.m.b.H.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
In this study the investigators aim to test whether an evidence based probiotic is able to revert proton pump inhibitor induced dysbiosis of the gut microbiome.
Detailed Description
With the emergence of high throughput sequencing techniques, researchers obtained the necessary tools to launch in-depth investigations into the structure and function of the intestinal microbiome. For the first time, it was possible to describe the influence of genetics, environment, nutrition and diseases on the microbiome and identify major determinants. One of the most prominent influencing factors on the composition of the microbiome is the use of proton pump inhibitors (PPI), in the general population as well as in chronic diseases, such as liver cirrhosis. Proton pump inhibitors are used to treat gastric acid related diseases. They drastically reduce the secretion of gastric acid and thereby increase the gastric pH. The reduction of gastric acid production, however, allows acid-sensitive food-borne and oral bacteria to pass the stomach unharmed and colonize the more distal parts of the intestine. In addition, PPI use creates less favorable conditions for typical gut commensals and reduces the microbial diversity in the intestine. These alterations in the microbiome can be linked to PPI side effects, such as gastrointestinal symptoms (e.g., abdominal discomfort, bloating, constipation or diarrhea) and an increased risk for enteral infections. In patients with liver cirrhosis, PPI-induced changes in the microbiome, namely Streptococcus salivarius and Veillonella parvula - two oral bacteria, are linked to intestinal inflammation and gut permeability and predict a higher risk of complications and a higher three-year liver related mortality. These are considerable risks that need to be weighed against the benefits of the therapy. Reduction of PPI use to cases with a clear indication is one important measure to reduce potential harm of the treatment. However, many patients require long-term treatment, e.g. for gastroesophageal reflux disease or to prevent gastrointestinal bleeding when drugs with a high risk of bleeding are used (such as thrombocyte aggregation inhibitors and oral anticoagulation). Therefore, strategies to reduce oralization and thereby symptoms and negative consequences of PPI are necessary. One possibility to change the composition of the gut microbiome is the use of probiotic bacteria. Probiotics are live microorganisms that have been demonstrated to alter the gut microbiome and exhibit positive effects on numerous gastrointestinal complaints, strengthen the gut barrier and reduce inflammation parameters. The investigators previously showed in a pilot study that a multispecies probiotic was able to improve gut permeability biomarkers in patients with long-term PPI therapy as well as gastrointestinal symptoms. However, this product was not able to efficiently reverse oralization. Therefore, the investigators conducted a series of experiments, including direct and indirect pathogen inhibition tests to identify probiotic strains that are capable of inhibiting the growth of Streptococcus salivarius and Veillonella parvula in vitro to design an evidence based probiotic mixture. The investigators screened 43 QPS (Qualified presumption of safety, granted by the European Food Safety Authority) certified probiotic strains and identified 5 strains as potential therapeutic agents to prevent/treat PPI induced oralization (unpublished data).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dysbiosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
unblinded longitudinal study will be performed
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
The study product contains Lactobacillus acidophilus W53, Lactobacillus acidophilus W55, Lactobacillus casei W56, Lactobacillus plantarum W1, Lactobacillus plantarum W21, Lactobacillus rhamnosus W71, and Pediococcus acidilactici W143.
Intervention Type
Dietary Supplement
Intervention Name(s)
Intervention
Intervention Description
multispecies probiotic
Primary Outcome Measure Information:
Title
Changes in overall symptom score
Description
Gastrointestinal quality of life index (GIQLI)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Other dimension of gastrointestinal quality of life
Description
Gastrointestinal quality of life index (GIQLI)
Time Frame
3 months
Title
Composition of the faecal metabolome
Description
NMR metabolomics
Time Frame
3 months
Title
Zonulin
Description
measurement of faecal zonulin
Time Frame
3 months
Title
Calprotectin
Description
measurement of faecal calprotectin
Time Frame
3 months
Title
Diaminooxidase
Description
measurement of serum diaminooxidase
Time Frame
3 months
Title
lipopolysaccharide binding protein
Description
measurement of serumlipopolysaccharide binding protein
Time Frame
3 months
Title
soluble CD14
Description
measurement of serum soluble CD14
Time Frame
3 months
Title
Veillonella parvula
Description
measurement of stool Veillonella parvula gene abundance
Time Frame
3 months
Title
Streptococcus salivarius
Description
measurement of stool Streptococcus salivarius gene abundance
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >18; Signed Informed Consent; PPI intake for at least 3 months; Willing to accept use of all encoded data, including publication, and the confidential use and storage of all data for at least 15 years; Exclusion criteria Diagnosed with a gastrointestinal infection within 4 weeks prior to screening; Severe gastrointestinal disorders (e.g. inflammatory bowel diseases) Received any of the following products/medication prior to screening: systemic antibiotics, prokinetics, prebiotic supplements, probiotic supplements within 4 weeks prior to screening; Concomitant diseases or other circumstances that suggest that the patients are not eligible for participation in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vanessa Stadlbauer, Association Prof Dr
Phone
0043 316
Ext
385
Email
vanessa.stadlbauer@medunigraz.at
Facility Information:
Facility Name
Medical University Graz
City
Graz
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vanessa Stadlbauer-Köllner, MD
Phone
0043 316 385
Ext
82282
Email
vanessa.stadlbauer@medunigraz.at

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Microbiome data will be shared in a public repository, other data will depend on results and IPR discussions between partners
IPD Sharing Time Frame
Microbiome data will be shared in a public repository when the paper will be submitted, other data will depend on results and IPR discussions between partners

Learn more about this trial

Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Dysbiosis

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