Functional DyspepsiaPhase 4CLARIFYNCT01373970
The Clinical Significance of Acid Rebound in Functional Dyspepsia
A Phase 4 study of Functional Dyspepsia, run by Zealand University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Functional Dyspepsia
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 184 participants
- Where
- 1 siteDenmark
- Study dates
- May 2011to Sep 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptoms indicating dyspepsia, including:
- Epigastric pain or epigastric discomfort
- Bothersome postprandial fullness
- Early satiation
- Epigastric burning
- Access to internet
Who cannot join
- 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)
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- 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 locations and contacts
1 site in 1 country.
About this study
Official title: The Clinical Significance of Acid Rebound: Symptoms of Reflux After PPI Treatment in Patients With Functional Dyspepsia
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.
Read more
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
- Being tested
- Placebo, Pantoprazole + Placebo
- Keywords
- Functional Dyspepsia, Protonpump inhibitor, Rebound Acid HyperSecretion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo, one tablet daily for 12 weeks
Pantoprazole + PlaceboDrug
Pantoprazole 40 mg, one tablet daily in eight weeks followed by a blinded cross over to placebo, one tablet daily for four weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| PPI + Placebo | Active comparator | PPI followed by cross over to placebo Receives: Drug: Pantoprazole + Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: week 9 - 12
Secondary outcomes (7)
Use of escape medication
Difference in use of escape medication in weeks 9 - 12 between PPI- and placebo group
Measured: Week 9 - 12
Endoscopic findings
Number of study subjects who have esophagitis, peptic stricture or Barrett's esophagus at inclusion without having symptoms of reflux.
Measured: 0 - 2 weeks before inclusion
pH monitoring
Number of study subject who have an abnormal pH monitoring at inclusion with-out symptoms of reflux
Measured: 0 - 2 weeks before inclusion
Irritable Bowel Syndrome (IBS)
Number of study subjects with ROME III score indicating IBS at inclusion
Measured: 0 - 2 weeks before inclusion
Irritable Bowel Syndrome (IBS) and treatment
Difference in symptom scores between study subjects with and without IBS in the PPI- and placebo group in weeks 0 - 12
Measured: Week 0 - 12
Effect of PPI on Functional Dyspepsia
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.
Measured: Week 8
Helicobacter Pylori
Difference in symptom score for subject with and without H. Pylori between PPI- and placebo group in weeks 9 - 12.
Measured: Week 9 - 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2011 (estimated)
- Study startMay 2011
- Primary completionMay 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Functional DyspepsiaStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anders Bergh Loedrup, Zealand University Hospital
- Investigators
- Anders B. Lødrup, MD, Principal investigator, Zealand University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01373970
- Sponsor's protocol ID
- SJ-217
- Acronym
- CLARIFY
- Status last verified
- Dec 2013
- First submitted
- 17 May 2011
- Last updated
- 6 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Clinical Significance of Acid Rebound: Symptoms of Reflux After PPI Treatment in Patients With Functional Dyspepsia
- ClinicalTrials.gov ID
- NCT01373970
- Acronym / sponsor ID
- CLARIFY / SJ-217
- Conditions
- Functional Dyspepsia
- Keywords
- Functional Dyspepsia, Protonpump inhibitor, Rebound Acid HyperSecretion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 184 participants (actual)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- May 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 15 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| PPI + Placebo | Active comparator | Drug: Pantoprazole + PlaceboPPI followed by cross over to placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Symptoms indicating dyspepsia, including:
- Access to internet
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo, one tablet daily for 12 weeks | Drug | Placebo |
| Pantoprazole + PlaceboPantoprazole 40 mg, one tablet daily in eight weeks followed by a blinded cross over to placebo, one tablet daily for four weeks | Drug | PPI + Placebo |
Primary outcome
Development of GERD
Time frame: week 9 - 12
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.
7 secondary outcomes
Use of escape medication
Time frame: Week 9 - 12
Endoscopic findings
Time frame: 0 - 2 weeks before inclusion
pH monitoring
Time frame: 0 - 2 weeks before inclusion
Irritable Bowel Syndrome (IBS)
Time frame: 0 - 2 weeks before inclusion
Irritable Bowel Syndrome (IBS) and treatment
Time frame: Week 0 - 12
Effect of PPI on Functional Dyspepsia
Time frame: Week 8
Helicobacter Pylori
Time frame: Week 9 - 12
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anders B. Lødrup, MD principal investigator
Zealand University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Functional Dyspepsia, run by Zealand University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of GERD (time frame: week 9 - 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2013.