Gastroesophageal Reflux DiseasePhase 2/3NCT00539240
Role of Pain Modulation in GERD Patients Who Failed Standard Dose PPI
A Phase 2/3 study of Gastroesophageal Reflux Disease, run by US Department of Veterans Affairs at 1 site in United States.
Trial summary
The purpose of this project is to compare the efficacy (how successful) 1) standard-dose proton pump inhibitor (PPI) (rabeprazole 20 mg once daily) (a medication that completely blocks the stomach from producing acid) plus low dose tricyclic antidepressant (nortriptyline 50mg) (TCA); 2) double-dose PPI (rabeprazole 20… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Gastroesophageal Reflux Disease
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 236 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Nov 2011
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Currently being treated with a PPI, but continue to experience GERD symptoms (such as heartburn) at least 2 times per week.
Who cannot join
- Known allergy or intolerance to TCA
- History of serious arrhythmia or use of anti-arrhythmics
- History of seizures
- Subjects with significant co-morbidity, e.g., cardiovascular, respiratory, urogenital, renal, gastrointestinal, hepatic, hematological, endocrine, neurologic or psychiatric
- With evidence or history of drug abuse within the past 6 months
- Erosive esophagitis, esophageal ulceration, peptic stricture, Barrett's esophagus or adenocarcinoma of the esophagus on endoscopy
Show all 11Show fewer
- History of esophagogastric surgery
- Gastric or duodenal lesions (ulcer, tumor, etc.)
- Women who are pregnant or of childbearing age who are not on contraception
- Patients who are unwilling or unable to provide informed consent
- Insulin dependent diabetes
Trial locations and contacts
1 site in 1 country.
United States1 site
Southern Arizona VA Health Care System, Tucson
Tucson, Arizona, 85723
About this study
The purpose of this project is to compare the efficacy (how successful) 1) standard-dose proton pump inhibitor (PPI) (rabeprazole 20 mg once daily) (a medication that completely blocks the stomach from producing acid) plus low dose tricyclic antidepressant (nortriptyline 50mg) (TCA); 2) double-dose PPI (rabeprazole 20 mg twice a day); to 3) standard-dose PPI (rabeprazole 20mg once daily) and placebo (an inactive substance, like a sugar pill) to determine the relative symptom resolution and health-related quality of life in gastroesophageal reflux disease (a disease characterized by a burning sensation (heartburn) behind the breast bone caused by a backflow of stomach contents into the esophagus) (GERD) patients who fail standard-dose PPI and you will be randomly assigned (similar to flipping a coin) to one of the three groups.
Read the detailed description
Failure of standard dose PPI to control GERD symptoms has been increasingly encountered in clinical practice (both primary care and sub-specialties) and has become one of the most challenging therapeutic dilemmas in GERD management. It has been estimated that up to 30% of the patients receiving PPI once daily will continue to report typical GERD symptoms [1]. Presently, increasing the PPI dose has been the standard of care in these patients [2]. However, success in relieving refractory GERD symptoms with such a therapeutic approach has been extremely limited, resulting in frustration of both the patient as well as the health care provided. Furthermore, patients who fail PPI will continue to seek medical attention and may undergo a variety of invasive or non-invasive tests, and thus consume already limited health care resources. Recent advancement in the understanding of the diverse composition of the different GERD groups as well as symptom generation has led to the recognition of alteration in pain perception as an important contributing factor for PPI failure in some and the presence of non-acid related stimuli in others [3].
This study will clarify for the first time the role of pain modulation in patients who failed standard dose of PPI. The clinical experience with doubling the PPI dose, which is the current standard of care, has been very limited and relatively disappointing. Additionally, this study may identify the group of PPI failure patients that may benefit from doubling the dose of PPI and the group that will benefit more from adding a pain modulator. This study is timely, has never been performed and addresses a prevalent emerging clinical dilemma in GI as well as primary care clinics.
- Conditions
- Gastroesophageal Reflux Disease
- Being tested
- Rabeprazole 20mg, placebo dinner and bedtime, Rabeprazole 20 mg two times, Placebo at bedtime, Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant
- Keywords
- acid reflux, acid regurgitation, esophagitis, GERD, heartburn, pain, peptic
- Medical subject headings
- Gastroesophageal Reflux, Esophagitis, Heartburn, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rabeprazole 20mg, placebo dinner and bedtimeDrug
Also called AcipHex
Breakfast study medication - Rabeprazole 20mg, matching placebo at dinner , Placebo for tricyclic antidepressant at bedtime
Rabeprazole 20 mg two times, Placebo at bedtimeDrug
Also called Aciphex
Breakfast \& Dinner study medication - Rabeprazole, placebo for tricyclic antidepressant at bedtime
Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic AntidepressantDrug
Also called Nortriptyline and Aciphex
Rabeprazole (Breakfast) study medication, dinner placebo medication, tricyclic antidepressant at bedtime
| Study group | Role | What they receive |
|---|---|---|
| Rabeprazole morning/evening placebo bedtime | Placebo comparator | AciPhex 20 mg BID and once daily placebo Receives: Drug: Rabeprazole 20 mg two times, Placebo at bedtime |
| Rabeprazole breakfast, placebo dinner and bedtime | Placebo comparator | AcipHex 20 mg once daily and BID placebo Receives: Drug: Rabeprazole 20mg, placebo dinner and bedtime |
| Rabeprazole breakfast, placebo dinner, nortriptyline bedtime | Active comparator | AcipHex 20 mg once daily, placebo once daily and nortriptyline once daily Receives: Drug: Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daytime Heartburn, Number of Days in Week Symptoms Intensity Score < 3 (Better)
the number of days with Symptom Intensity Score < 3 (better) for daytime heartburn during week 6 as compared to baseline
Measured: Symptom control after 6 weeks of treatment
Nighttime Heartburn, Number of Days in Week Symptom Activity Score <3 (Better) in Week 6 Compared to Baseline
the number of days with Symptom Intensity Score < 3 (better) for nighttime heartburn during week 6 as compared to baseline
Measured: Symptom control after 6 weeks of treatment
Acid Regurgitation, Number of Days in Week Symptoms Intensity Score < 3 (Better)
the number of days with Symptom Intensity Score < 3 (better) for acid regurgitation during week 6 as compared to baseline
Measured: Symptom control after 6 weeks of treatment
Secondary outcomes (1)
Health Related Quality of Life
SF-36 Physical Component Score (higher number better quality of life), is a measure of overall physical quality of life distinct from mental health. The range is 0 - 100. It has been adjusted to US national norms so that a score of 50 corresponds to the national mean.
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2007 (estimated)
- Study startApr 2006
- Primary completionApr 2010
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastroesophageal Reflux DiseaseStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 236 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00539240
- Sponsor's protocol ID
- CLIN-022-04F
- Status last verified
- Jul 2014
- First submitted
- 3 Oct 2007
- Last updated
- 18 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Pain Modulation in GERD Patients Who Failed Standard Dose PPI
- ClinicalTrials.gov ID
- NCT00539240
- Acronym / sponsor ID
- CLIN-022-04F
- Conditions
- Gastroesophageal Reflux Disease
- Keywords
- acid reflux, acid regurgitation, esophagitis, GERD, heartburn, pain, peptic
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 236 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Apr 2006
- Primary completion
- Apr 2010 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 4 Oct 2007 (estimated)
- Results
- Posted 18 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this project is to compare the efficacy (how successful) 1) standard-dose proton pump inhibitor (PPI) (rabeprazole 20 mg once daily) (a medication that completely blocks the stomach from producing acid) plus low dose tricyclic antidepressant (nortriptyline 50mg) (TCA); 2) double-dose PPI (rabeprazole 20 mg twice a day); to 3) standard-dose PPI (rabeprazole 20mg once daily) and placebo (an inactive substance, like a sugar pill) to determine the relative symptom resolution and health-related quality of life in gastroesophageal reflux disease (a disease characterized by a burning sensation (heartburn) behind the breast bone caused by a backflow of stomach contents into the esophagus) (GERD) patients who fail standard-dose PPI and you will be randomly assigned (similar to flipping a coin) to one of the three groups.
Detailed description
Failure of standard dose PPI to control GERD symptoms has been increasingly encountered in clinical practice (both primary care and sub-specialties) and has become one of the most challenging therapeutic dilemmas in GERD management. It has been estimated that up to 30% of the patients receiving PPI once daily will continue to report typical GERD symptoms [1]. Presently, increasing the PPI dose has been the standard of care in these patients [2]. However, success in relieving refractory GERD symptoms with such a therapeutic approach has been extremely limited, resulting in frustration of both the patient as well as the health care provided. Furthermore, patients who fail PPI will continue to seek medical attention and may undergo a variety of invasive or non-invasive tests, and thus consume already limited health care resources. Recent advancement in the understanding of the diverse composition of the different GERD groups as well as symptom generation has led to the recognition of alteration in pain perception as an important contributing factor for PPI failure in some and the presence of non-acid related stimuli in others [3].
This study will clarify for the first time the role of pain modulation in patients who failed standard dose of PPI. The clinical experience with doubling the PPI dose, which is the current standard of care, has been very limited and relatively disappointing. Additionally, this study may identify the group of PPI failure patients that may benefit from doubling the dose of PPI and the group that will benefit more from adding a pain modulator. This study is timely, has never been performed and addresses a prevalent emerging clinical dilemma in GI as well as primary care clinics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rabeprazole morning/evening placebo bedtime | Placebo comparator | Drug: Rabeprazole 20 mg two times, Placebo at bedtimeAciPhex 20 mg BID and once daily placebo |
| Rabeprazole breakfast, placebo dinner and bedtime | Placebo comparator | Drug: Rabeprazole 20mg, placebo dinner and bedtimeAcipHex 20 mg once daily and BID placebo |
| Rabeprazole breakfast, placebo dinner, nortriptyline bedtime | Active comparator | Drug: Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic AntidepressantAcipHex 20 mg once daily, placebo once daily and nortriptyline once daily |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Currently being treated with a PPI, but continue to experience GERD symptoms (such as heartburn) at least 2 times per week.
Key exclusion criteria (11 listed)
- Known allergy or intolerance to TCA
- History of serious arrhythmia or use of anti-arrhythmics
- History of seizures
- Subjects with significant co-morbidity, e.g., cardiovascular, respiratory, urogenital, renal, gastrointestinal, hepatic, hematological, endocrine, neurologic or psychiatric
- With evidence or history of drug abuse within the past 6 months
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 |
|---|---|---|
| Rabeprazole 20mg, placebo dinner and bedtimeAlso: AcipHexBreakfast study medication - Rabeprazole 20mg, matching placebo at dinner , Placebo for tricyclic antidepressant at bedtime | Drug | Rabeprazole breakfast, placebo dinner and bedtime |
| Rabeprazole 20 mg two times, Placebo at bedtimeAlso: AciphexBreakfast \& Dinner study medication - Rabeprazole, placebo for tricyclic antidepressant at bedtime | Drug | Rabeprazole morning/evening placebo bedtime |
| Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic AntidepressantAlso: Nortriptyline and AciphexRabeprazole (Breakfast) study medication, dinner placebo medication, tricyclic antidepressant at bedtime | Drug | Rabeprazole breakfast, placebo dinner, nortriptyline bedtime |
Primary outcome
Daytime Heartburn, Number of Days in Week Symptoms Intensity Score < 3 (Better)
Time frame: Symptom control after 6 weeks of treatment
the number of days with Symptom Intensity Score < 3 (better) for daytime heartburn during week 6 as compared to baseline
Nighttime Heartburn, Number of Days in Week Symptom Activity Score <3 (Better) in Week 6 Compared to Baseline
Time frame: Symptom control after 6 weeks of treatment
the number of days with Symptom Intensity Score < 3 (better) for nighttime heartburn during week 6 as compared to baseline
Acid Regurgitation, Number of Days in Week Symptoms Intensity Score < 3 (Better)
Time frame: Symptom control after 6 weeks of treatment
the number of days with Symptom Intensity Score < 3 (better) for acid regurgitation during week 6 as compared to baseline
1 secondary outcome
Health Related Quality of Life
Time frame: end of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study of Gastroesophageal Reflux Disease, run by US Department of Veterans Affairs at 1 site in United States.
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 1 inclusion and 11 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: finished, as of the sponsor's last update on 18 Aug 2014. 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 United States. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Daytime Heartburn, Number of Days in Week Symptoms Intensity Score < 3 (Better) (time frame: Symptom control after 6 weeks of treatment). The study lists 3 primary outcomes in all. 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 18 Aug 2014.