Clinical trial NCT03220802: Probiotic Modulation of Intestinal Microbiota in Long-term Intake of Proton Pump Inhibitors
Official title: Probiotic Modulation of Intestinal Microbiota in Long-term Intake of Proton Pump Inhibitors: Influence on Intestinal Inflammation and Digestion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Patients on Long-term Proton Pump Inhibitor Therapy
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2017-07-18
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Changes in faecal calprotectin levels due to the intervention
timeFrame: 6 months
Secondary outcomes:
measure: changes in PPI associated Veillonella/Streptococcus dysbiosis index due to the intervention
timeFrame: 6 months
measure: Changes in faecal zonulin levels due to the intervention
timeFrame: 6 months
measure: Changes in serum endotoxin levels due to the intervention
timeFrame: 6 months
measure: Changes in serum lipopolysaccharide binding protein (LBP) levels due to the intervention
timeFrame: 6 months
measure: Changes in serum sCD14 levels due to the intervention
timeFrame: 6 months
measure: Changes in serum VitB12 levels due to the intervention
timeFrame: 6 months
measure: Changes in health related quality of life due to the intervention
timeFrame: 6 months
measure: Changes in gastrointestinal quality of life due to the intervention
timeFrame: 6 months
measure: Changes in nutritional behaviour due to the intervention
timeFrame: 6 months
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Internal Medicine, Medical University of Graz
Study officials:
References: