Proton Pump Inhibitors and Gastrointestinal Symptoms

Gastrointestinal Symptoms Clinical Trial

Official title:

Protective Effects of Probiotic Administration on SIBO Development and Bowel Symptom Onset in GERD Patients at Long-term PPI Treatment: a Randomized Controlled Cross-sectional Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02054455
• Other study ID #: PPI-SIBO-01
• Status: Completed
• Phase: Phase 4
• First received: April 11, 2012
• Last updated: February 3, 2014
• Start date: November 2012
• Est. completion date: November 2013

Study information

• Verified date: February 2014
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Gastrointestinal Diseases
• Gastrointestinal Symptoms
• Signs and Symptoms, Digestive
• Small Intestinal Overgrowth

Intervention

Dietary Supplement:
• Lactobacillus paracasei F19
25x10E9 live bacterial cells for 3 days/week for 6 months
• Placebo
Placebo will consist of a preparation similar to that of probiotic but with no added microorganisms.

Locations

Country	Name	City	State
Italy	University Federico Ii	Naples

Sponsors (3)

Lead Sponsor	Collaborator
Federico II University	Ospedale Nuovo Regina Margherita di Roma Dr. Salvatore Campo, University of Cantanzaro

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gastrointestinal symptom's assessment	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).	up to 6 months	No
Secondary	Bowel habit assessment	Subjects will record their bowel habits on validated diary cards, including every single stool and stool consistency. Stool consistency will be de?ned according to the Bristol Stool Form Scale (BSFS). Diary cards will be returned every four weeks.	up to 6 months	No