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Proton Pump Inhibitors and Gastrointestinal Symptoms

Phase 4
Completed
Conditions
Gastrointestinal Symptoms
Small Intestinal Overgrowth
Interventions
Dietary Supplement: Lactobacillus paracasei F19
Dietary Supplement: Placebo
Registration Number
NCT02054455
Lead Sponsor
Federico II University
Brief Summary

The aim of the study is to evaluate the potential protective effect of Lactobacillus paracasei subspecies paracasei F19 administration on bowel symptom onset in patients with gastro-esophageal reflux disease at long-term PPI treatment.

Detailed Description

Population and study design

After the approval of the Local Ethical Committee and informed consent of patients, we will consecutively enrol, according to the calculated power of the study, 80 outpatients, among those referred to the Institutional centers on account of recent onset of typical reflux symptoms (heartburn and regurgitation).

Exclusion criteria will be: age \<18 or \>70 yrs; pregnancy or breast-feeding; evidence of major concomitant diseases (i.e., tumors, cardiovascular disorders and hepatic and/or renal failure); use of PPIs or H2-antagonists, non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics in the previous 3 months; presence of Helicobacter pylori (H. pylori) infection; erosive esophagitis; presence of bowel symptoms such as bloating, flatulence, abdominal pain, diarrhea and constipation in the last 6 months or irritable bowel syndrome (IBS) according to Rome III criteria.

All patients will undergo upper endoscopy. Patients who will fulfill the entry criteria will be enrolled in the study.

These patients will be treated with pantoprazole 40 mg die for 6 months and they will be randomly assigned to 4 arms:

* the first arm will receive placebo for 3 days/week for 6 months;

* the second arm will receive LP-F19 in a dose of 25x109 live bacterial cells for 3 days/week for 6 months;

* the third arm will receive LP-F19 in a dose of 25x109 live bacterial cells for 3 days/week for the first three months and placebo 3 days/week for the following three months;

* the fourth arm will receive placebo 3 days/week for the first three months and LP-F19 in a dose of 25x109 live bacterial cells for 3 days/week for the following three months.

Placebo will consist of a preparation similar to that of probiotic but with no added microorganisms.

Adherence to treatment Will be evaluated based on self-reporting by the patients and count of returned sackets during monthly control visits. Patients who will take at least 90% of the drugs (pantoprazole, LP-F19 and placebo) for at least 90% of the scheduled time will be considered compliant.

Before starting therapy (i.e. baseline evaluation) and every 4 weeks, each patient will fill up a structured questionnaire for symptom assessment, concerning heartburn and regurgitation, as well as, bowel symptoms, including bloating, abdominal pain, flatulence and bowel habit.

Symptom and bowel habit assessment

Baseline and every 4 weeks after the beginning of the therapy, each patient will fill up a structured questionnaire, focusing on the presence of heartburn, regurgitation, bloating, flatulence, abdominal pain, diarrhea and constipation, with the help of a physician interviewer. The questionnaire, according to a Likert scale, will assess frequency (0 = never, 1 = \< 1 episode/week; 2 = \< 3 episodes/week; 3 = \> 3 episodes/week; 4 = daily episodes) and severity (0 = absent, 1 = mild i.e. not interfering with the daily activities, 2 = moderate i.e. limiting the daily activities, and 3 = severe i.e. hampering the daily activities) of each symptom during the previous 6 months, at baseline and during the last month at every 4-week checkpoints. According to an arbitrary index, symptoms will be considered significant when interfering with daily activities (i.e., mean total score, frequency plus severity, ≥ 4).

Subjects will record their bowel habit on validated diary cards, including every single stool and stool consistency. Stool consistency will be defined according to the Bristol Stool Form Scale (BSFS). Diary cards will be returned every four weeks.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria
  • recent onset of typical reflux symptoms (heartburn and regurgitation).
Exclusion Criteria
  • age <18 or >70 yrs
  • pregnancy or breast-feeding
  • evidence of major concomitant diseases (i.e., tumors, cardiovascular disorders and hepatic and/or renal failure)
  • use of PPIs or H2-antagonists, non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics in the previous 3 months
  • presence of Helicobacter pylori (H. pylori) infection
  • erosive esophagitis
  • presence of bowel symptoms such as bloating, flatulence, abdominal pain, diarrhea and constipation in the last 6 months or irritable bowel syndrome (IBS) according to Rome III criteria.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PPI and Lactobacillus paracasei F19 cross-over 1PlaceboPatients will receive placebo 3 days/week for the first three months and Lactobacillus paracasei F19 in a dose of 25x10E9 live bacterial cells for 3 days/week for the following three months
PPI and Lactobacillus paracasei F19 cross-over 2Lactobacillus paracasei F19Patients will receive Lactobacillus paracasei F19 in a dose of 25x10E9 live bacterial cells for 3 days/week for the first three months and placebo 3 days/week for the following three months
PPI and Lactobacillus paracasei F19 cross-over 2PlaceboPatients will receive Lactobacillus paracasei F19 in a dose of 25x10E9 live bacterial cells for 3 days/week for the first three months and placebo 3 days/week for the following three months
PPI and placeboPlaceboPatients will receive PPI and placebo for 3 days/week for 6 months
PPI and Lactobacillus paracasei F19Lactobacillus paracasei F19Patients will receive Lactobacillus paracasei F19 in a dose of 25x10E9 live bacterial cells for 3 days/week for 6 months
PPI and Lactobacillus paracasei F19 cross-over 1Lactobacillus paracasei F19Patients will receive placebo 3 days/week for the first three months and Lactobacillus paracasei F19 in a dose of 25x10E9 live bacterial cells for 3 days/week for the following three months
Primary Outcome Measures
NameTimeMethod
Gastrointestinal symptom's assessmentup to 6 months

The questionnaire used to assess symptoms was built-up according to a four-point Likert scale evaluating both frequency (0 = never, 1 = \< 1 episode/week; 2 = \< 3 episodes/week; 3 = \> 3 episodes/week; 4 = daily episodes) and severity (0 = absent, 1 = mild i.e. not interfering with the daily activities, 2 = moderate i.e. limiting the daily activities, and 3 = severe i.e. hampering the daily activities) of each symptom during the previous 6 months, at baseline and during the last month at every 4-week checkpoints. According to an arbitrary index, symptoms were considered significant when interfering with daily activities (i.e., mean total score, frequency plus severity, \>4).

Secondary Outcome Measures
NameTimeMethod
Bowel habit assessmentup to 6 months

Subjects will record their bowel habits on validated diary cards, including every single stool and stool consistency. Stool consistency will be defined according to the Bristol Stool Form Scale (BSFS). Diary cards will be returned every four weeks.

Trial Locations

Locations (1)

University Federico Ii

🇮🇹

Naples, Italy

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