Proton Pump Inhibitors and Gastrointestinal Symptoms
Condition: Gastrointestinal Symptoms; Small Intestinal Overgrowth
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Lactobacillus paracasei F19; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 25x10E9 live bacterial cells for 3 days/week for 6 months; Placebo will consist of a preparation similar to that of probiotic but with no added microorganisms.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: PPI; SIBO; LP-F19