Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Probiotic Modulation of Intestinal Microbiota in Long-term Intake of Proton Pump Inhibitors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03220802
Recruitment Status : Active, not recruiting
First Posted : July 18, 2017
Last Update Posted : November 20, 2019
Sponsor:
Information provided by (Responsible Party):
Medical University of Graz

Brief Summary:
Long-term proton pump inhibitor use has been linked to intestinal dysbiosis, inflammation and gastrointestinal symptoms. Probiotics has been shown to correct dysbiosis, reduce inflammation and strengthen the gut barrier. The aim of this study is to evaluate the influence of a three months intervention with a probiotic on intestinal inflammation, bowel symptoms, dysbiosis and gut permeability.

Condition or disease Intervention/treatment Phase
Patients on Long-term Proton Pump Inhibitor Therapy Dietary Supplement: OMNI-BiOTiC PPI Not Applicable

Detailed Description:

Proton pump inhibitors (PPIs) are among the top 5 most widely used drugs in the world. PPIs suppress the formation of gastric acid through the inhibition of hydrogen-potassium-adenosine-triphosphatase (H+ / K+ -ATPase) - a known proton pump in the parietal cells of the stomach. In practice, PPIs are commonly prescribed to treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They are also used prophylactically to prevent stress ulcers and to reduce GI toxicity associated with certain medications, including non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and steroids, sometimes despite a paucity of evidence. PPI use has been associated with increased risk of enteric infections. A meta-analysis of 23 studies, comprising almost 300.000 patients, showed a 65% increase in the incidence of Clostridium difficile-associated diarrhoea among patients who used PPIs. Another meta-analysis of 11.280 patients, from six studies evaluating Salmonella, Campylobacter and other enteric infections, also found an increased risk due to acid suppression, with a greater association with PPI than with H2-receptor antagonists. Moreover, long term PPI use has been shown to be associated with bowel symptoms: A study from 2011 reported incidences of bloating, flatulence, abdominal pain and diarrhoea (43%, 17%, 7% and 2% of selected cases, respectively). In addition, PPIs are known to cause malabsorption of Vitamin B12 which may ultimately lead to Vitamin B12 deficiency. Very recently, PPI use was associated with an increase in mortality.

The gut microbiome plays an important role in enteric infections and bowel symptoms. The composition of the gut microbiome can inhibit or promote the microbial colonisation of the gut by microbial pathogens. Several mechanisms can influence bacterial growth or the immune system.

Long term PPI use is associated with profound changes in the gut microbiome. It is believed that these conditions are caused through the long-term suppression of gastric acid secretion (and thus shifting intragastric pH) which alters the natural habitat of resident microbiota. Furthermore, increased gastric pH might not sufficiently protect against oral or food-borne pathogens. We recently conducted a study at the Medical University of Graz where we could show that patients with long-term PPI therapy have dysbiosis associated with intestinal inflammation, increased gut permeability, bacterial translocation and systemic inflammation associated with a higher risk of complications and mortality in liver cirrhosis. (A. Horvath et al., Long-term proton pump inhibitor use increases intestinal dysbiosis, gut permeability, inflammation and mortality in patients with liver cirrhosis, UEG Journal, accepted) Probiotics are live microorganisms that have been demonstrated to alter gut flora and exhibit positive effects on numerous gastrointestinal complaints, strengthen the gut barrier and reduce inflammation parameters

We hypothesize that a three months probiotic intervention with OMNi BiOTiC PPI improves PPI induced dysbiosis, intestinal inflammation and gut permeability in patients on long term PPI therapy, leading to a decrease in bacterial translocation and a better gastrointestinal quality of life.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Probiotic Modulation of Intestinal Microbiota in Long-term Intake of Proton Pump Inhibitors: Influence on Intestinal Inflammation and Digestion
Actual Study Start Date : September 22, 2017
Actual Primary Completion Date : July 17, 2018
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
Experimental: Test group
participants receive a daily dose of OMNI-BiOTiC PPI for three months
Dietary Supplement: OMNI-BiOTiC PPI
The study product consists of a sachet containing 4g of yellowish powder made of corn starch, maltodextrin, fructo-oligosaccharide P6, inulin P2, vegetable protein and 12 bacterial strains (Bacillus coagulans W183, Bacillus subtilus W201, Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, Lactobacillus acidophilus W22, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, Propionibacterium freudenreichii W200, Lactobacillus rhamnosus W71, in a concentration of 2 x 109 cfu/g).




Primary Outcome Measures :
  1. Changes in faecal calprotectin levels due to the intervention [ Time Frame: 6 months ]
    Calprotectin levels are measured in ng/mg stool using enzyme linked immunosorbent assay (ELISA) at baseline, after 3 months of intervention and after further 3 months of follow up


Secondary Outcome Measures :
  1. changes in PPI associated Veillonella/Streptococcus dysbiosis index due to the intervention [ Time Frame: 6 months ]
    relative abundance of bacteria in the gut microbiome will be assessed using 16S DNA sequencing, bacteria from the oral cavity will be especially investigated at baseline, after 3 months of intervention and after further 3 months of follow up

  2. Changes in faecal zonulin levels due to the intervention [ Time Frame: 6 months ]
    Zonulin levels are measured in ng/mg stool using enzyme linked immunosorbent assay (ELISA) at baseline, after 3 months of intervention and after further 3 months of follow up

  3. Changes in serum endotoxin levels due to the intervention [ Time Frame: 6 months ]
    endotoxin levels are measured in endotoxin units/ml serum using a cell based detection method at baseline, after 3 months of intervention and after further 3 months of follow up

  4. Changes in serum lipopolysaccharide binding protein (LBP) levels due to the intervention [ Time Frame: 6 months ]
    LBP levels are measured in µg/ml serum using ELISA at baseline, after 3 months of intervention and after further 3 months of follow up

  5. Changes in serum sCD14 levels due to the intervention [ Time Frame: 6 months ]
    sCD14 levels are measured in µg/ml serum using ELISA at baseline, after 3 months of intervention and after further 3 months of follow up

  6. Changes in serum VitB12 levels due to the intervention [ Time Frame: 6 months ]
    VitB12 levels are measured as part of the routine laboratory report at baseline, after 3 months of intervention and after further 3 months of follow up

  7. Changes in health related quality of life due to the intervention [ Time Frame: 6 months ]
    Quality of life will be described using the Short Form 36 Questionnaire at baseline, after 3 months of intervention and after further 3 months of follow up

  8. Changes in gastrointestinal quality of life due to the intervention [ Time Frame: 6 months ]
    gastrointestinal quality of life will be described using the GIQLI questionnaire according to Eyparsch at baseline, after 3 months of intervention and after further 3 months of follow up

  9. Changes in nutritional behaviour due to the intervention [ Time Frame: 6 months ]
    Changes in nutritional behaviour due to the intervention will be determined by a food frequency questionnaire at baseline, after 3 months of intervention and after further 3 months of follow up



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >18
  • willing to give written Informed Consent
  • PPI intake for at least 6 months

Exclusion Criteria:

  • Active infections at time of inclusion
  • Antibiotic therapy within the last 14 days (includes prophylactic use)
  • Inflammatory bowel diseases
  • Consumption of pre/synbiotics other than the product provided during the trial
  • Concomitant diseases or other circumstances that suggest that the patients are not eligible for participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03220802


Locations
Layout table for location information
Austria
Department of Internal Medicine, Medical University of Graz
Graz, Austria, 8010
Sponsors and Collaborators
Medical University of Graz

Layout table for additonal information
Responsible Party: Medical University of Graz
ClinicalTrials.gov Identifier: NCT03220802     History of Changes
Other Study ID Numbers: Probiotics and PPI
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: November 20, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action