The Clinical Significance of Acid Rebound in Functional Dyspepsia

Overview[ - collapse ][ - ]

Purpose 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.
ConditionFunctional Dyspepsia
InterventionDrug: Placebo
Drug: Pantoprazole + Placebo
PhasePhase 4
SponsorUniversity Hospital Koge
Responsible PartyUniversity Hospital Koge
ClinicalTrials.gov IdentifierNCT01373970
First ReceivedMay 17, 2011
Last UpdatedDecember 5, 2013
Last verifiedDecember 2013

Tracking Information[ + expand ][ + ]

First Received DateMay 17, 2011
Last Updated DateDecember 5, 2013
Start DateMay 2011
Estimated Primary Completion DateSeptember 2013
Current Primary Outcome MeasuresDevelopment 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.
Current Secondary Outcome Measures
  • 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.

Descriptive Information[ + expand ][ + ]

Brief TitleThe Clinical Significance of Acid Rebound in Functional Dyspepsia
Official TitleThe Clinical Significance of Acid Rebound: Symptoms of Reflux After PPI Treatment in Patients With Functional Dyspepsia
Brief Summary
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
ConditionFunctional Dyspepsia
InterventionDrug: Placebo
Placebo, one tablet daily for 12 weeks
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
Study Arm (s)
  • Placebo Comparator: Placebo
  • Active Comparator: PPI + Placebo
    PPI followed by cross over to placebo

Recruitment Information[ + expand ][ + ]

Recruitment StatusTerminated
Estimated Enrollment184
Estimated Completion DateSeptember 2013
Estimated Primary Completion DateMay 2013
Eligibility Criteria
Inclusion Criteria:

- Symptoms indicating dyspepsia, including:

- Epigastric pain or epigastric discomfort

- Bothersome postprandial fullness

- Early satiation

- Epigastric burning

- Access to internet

Exclusion Criteria:

- Daily use of PPI or H2-receptor antagonists in more than 28 days within the last 120
days OR more than two days within the last 28 days OR more than five non-consecutive
days within the last 28 days.

- Mild heartburn or regurgitation more than once per week

- Moderate or severe heartburn or regurgitation at least once per week

- Complications to GERD (esophagitis, stricture or Barrett's esophagus) prior to
enrolment or at screening

- Abnormal findings at upper endoscopy necessitating treatment

- Abnormal pH-monitoring prior to enrolment or at screening (pH <4 in ≥5.5 % of the
time on "worst day" of 48-h monitoring)

- Excludes data from analysis regarding primary endpoint (see summary)

- Previous surgery on esophagus, stomach or duodenum

- Regular use of NSAIDs through the last six months

- Potential language problems in understanding information and registering symptoms

- Pregnancy or breast feeding

- Other diseases which can interfere with the symptom registration (severe congestive
heart disease, malignant disease, schizophrenia ect.)

- Abuse of alcohol/narcotics

- Allergy/intolerance to gelatine or lactose used in placebo

- Patients with pacemaker, Implantable Cardioverter Defibrillator or Implantable
Neurostimulator
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesDenmark

Administrative Information[ + expand ][ + ]

NCT Number NCT01373970
Other Study ID NumbersSJ-217
Has Data Monitoring CommitteeYes
Information Provided ByUniversity Hospital Koge
Study SponsorUniversity Hospital Koge
CollaboratorsNot Provided
Investigators Principal Investigator: Anders B. Lødrup, MD Koege Sygehus
Verification DateDecember 2013

Locations[ + expand ][ + ]

Koege Hospital
Koege, Denmark, 4600