The Clinical Significance of Acid Rebound in Functional Dyspepsia

NCT01373970 | Terminated Phase 4 DMC

• 1 other identifier: SJ-217
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

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.

Conditions

Functional Dyspepsia

Keywords

Functional Dyspepsia; Protonpump inhibitor; Rebound Acid HyperSecretion

Outcome Measures

Primary Outcomes (1)

• Development of GERD

  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.

  week 9 - 12

Secondary Outcomes (7)

• Use of escape medication

  Week 9 - 12

• Endoscopic findings

  0 - 2 weeks before inclusion

• pH monitoring

  0 - 2 weeks before inclusion

• Irritable Bowel Syndrome (IBS)

  0 - 2 weeks before inclusion

• Irritable Bowel Syndrome (IBS) and treatment

  Week 0 - 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

PPI + Placebo

ACTIVE COMPARATOR

PPI followed by cross over to placebo

Drug: Pantoprazole + Placebo

Interventions

Placebo DRUG

Placebo, one tablet daily for 12 weeks

Placebo

Pantoprazole + Placebo DRUG

Pantoprazole 40 mg, one tablet daily in eight weeks followed by a blinded cross over to placebo, one tablet daily for four weeks

PPI + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptoms indicating dyspepsia, including:
• Epigastric pain or epigastric discomfort
• Bothersome postprandial fullness
• Early satiation
• Epigastric burning
• Access to internet

You may not qualify if:

• 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

Sponsors & Collaborators

• Zealand University Hospital: lead

Study Sites (1)

Koege Hospital

Koege, 4600, Denmark

Location

MeSH Terms

Interventions

Pantoprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Anders B. Lødrup, MD

  Zealand University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: May 17, 2011
• First Posted: June 15, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: September 1, 2013
• Last Updated: December 6, 2013

Record last verified: 2013-12

Locations

DK (1)