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The Clinical Significance of Acid Rebound in Functional Dyspepsia (CLARIFY)

Z

Zealand University Hospital

Status and phase

Terminated
Phase 4

Conditions

Functional Dyspepsia

Treatments

Drug: Pantoprazole + Placebo
Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

Details and patient eligibility

About

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.

Enrollment

184 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

184 participants in 2 patient groups, including a placebo group

Placebo
Placebo Comparator group
Treatment:
Drug: Placebo
PPI + Placebo
Active Comparator group
Description:
PPI followed by cross over to placebo
Treatment:
Drug: Pantoprazole + Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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