The Clinical Significance of Acid Rebound in Functional Dyspepsia (CLARIFY)
Proton pump inhibitors (PPI) have been shown to cause acid reflux related symptoms at withdrawal in healthy volunteers, a phenomenon known as Rebound Acid Hyper Secretion. Whether this also applies for patients with dyspeptic symptoms but without true reflux disease (functional dyspepsia) treated with PPI is unknown. If this is the case, it could lead to an unfortunate long term use of PPI, since the acid rebound renders withdrawal too difficult.
This is a single centre, randomized, double-blinded, placebo-controlled cross over study. Study period is 12 weeks per study subject. Study subjects are referred to the study from General Practitioner (GP) and the gastroenterology department or endoscopy clinic of the investigational centre.
The study population consists of patients who seek their GP because of dyspepsia without alert signs, and whom the GP may consider starting on PPI. Out patients referred to the gastroenterology department or endoscopy clinic of the investigational centre because of dyspepsia without specific exclusion criteria are also invited to participate.
Baseline interview, upper endoscopy and pH monitoring are performed one week before inclusion to exclude patients with GERD. Helicobacter Pylori (Hp.) status is assessed by Helicobacter Urease Test (HUT). Hp. positive subjects without ulcus are not excluded.
Patients with a positive pH monitoring will not be included in the analysis regarding the primary endpoint (Development of GERD) but will be included in the analysis regarding one of the secondary endpoints (Effect of PPI on Functional Dyspepsia).
Study subjects are randomized to either pantoprazol followed by cross over to placebo or to placebo. Escape medication in the form of Gaviscon can be used on demand.
Internet based questionnaires are answered weekly. Questionnaires consist of the Gastrointestinal Symptom rating Scale (GSRS) in combination with items assessing postprandial fullness and items assessing the Montreal Criteria for Gastro Esophageal Reflux Disease (GERD).
Compliance to protocol is assessed at hospital visits every fourth week. At the end of study endoscopy and pH monitoring are repeated.
Drug: Pantoprazole + Placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||The Clinical Significance of Acid Rebound: Symptoms of Reflux After PPI Treatment in Patients With Functional Dyspepsia|
- Development of GERD [ Time Frame: week 9 - 12 ] [ Designated as safety issue: No ]Comparison of number of study subjects that develop GERD according to the Montreal definition including endoscopic findings and pH monitoring in weeks 9-12 in the PPI group versus the placebo group.
- Use of escape medication [ Time Frame: Week 9 - 12 ] [ Designated as safety issue: No ]Difference in use of escape medication in weeks 9 - 12 between PPI- and placebo group
- Endoscopic findings [ Time Frame: 0 - 2 weeks before inclusion ] [ Designated as safety issue: No ]Number of study subjects who have esophagitis, peptic stricture or Barrett's esophagus at inclusion without having symptoms of reflux.
- pH monitoring [ Time Frame: 0 - 2 weeks before inclusion ] [ Designated as safety issue: No ]Number of study subject who have an abnormal pH monitoring at inclusion with-out symptoms of reflux
- Irritable Bowel Syndrome (IBS) [ Time Frame: 0 - 2 weeks before inclusion ] [ Designated as safety issue: No ]Number of study subjects with ROME III score indicating IBS at inclusion
- Irritable Bowel Syndrome (IBS) and treatment [ Time Frame: Week 0 - 12 ] [ Designated as safety issue: No ]Difference in symptom scores between study subjects with and without IBS in the PPI- and placebo group in weeks 0 - 12
- Effect of PPI on Functional Dyspepsia [ Time Frame: Week 8 ] [ Designated as safety issue: No ]Number of study subjects in the PPI group versus the placebo group that answer "no discomfort at all" or "slight discomfort" to dyspepsia related questions ("ache/pain in the upper part of the abdomen" and "hunger pains/hollow feeling in the stomach") in week 8.
- Helicobacter Pylori [ Time Frame: Week 9 - 12 ] [ Designated as safety issue: No ]Difference in symptom score for subject with and without H. Pylori between PPI- and placebo group in weeks 9 - 12.
|Study Start Date:||May 2011|
|Study Completion Date:||September 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
Placebo, one tablet daily for 12 weeks
Active Comparator: PPI + Placebo
PPI followed by cross over to placebo
Drug: Pantoprazole + Placebo
Pantoprazole 40 mg, one tablet daily in eight weeks followed by a blinded cross over to placebo, one tablet daily for four weeks