Comparison of Acid Reflux at Two Levels in the Esophagus Using the BRAVO Capsule
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|ClinicalTrials.gov Identifier: NCT00579410|
Recruitment Status : Completed
First Posted : December 24, 2007
Last Update Posted : March 22, 2011
|First Submitted Date||December 21, 2007|
|First Posted Date||December 24, 2007|
|Last Update Posted Date||March 22, 2011|
|Study Start Date||May 2004|
|Actual Primary Completion Date||October 2009 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures
||This pilot project will attempt to study the level of acid exposure in the distal esophagus and proximal stomach of patients and correlate it with their symptoms. [ Time Frame: 24 hour period ]|
|Original Primary Outcome Measures||Same as current|
|Change History||Complete list of historical versions of study NCT00579410 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures
||To note patient satisfaction and comfort during the pH monitoring process. [ Time Frame: 7 days ]|
|Original Secondary Outcome Measures
||To note patient satifaction and comfort during the pH monitoring process. [ Time Frame: 7 days ]|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title||Comparison of Acid Reflux at Two Levels in the Esophagus Using the BRAVO Capsule|
|Official Title||Evaluation of Esophageal and Gastric Acid Levels in Patients Presenting With Upper Gastrointestinal Symptoms Using a Novel PH System|
|Brief Summary||The purpose of this research is to study the level of acid exposure above the gastroesophageal junction and the distal esophagus in patients with reflux symptoms using a capsule type acid measurement system. Patients with reflux symptoms are likely to have more acid reflux just above the junction of the stomach and the esophagus that may help to improve the diagnosis of gastroesophageal reflux disease (GERD). This may help better treat the reflux symptoms.|
Upper gastrointestinal symptoms and diseases, specifically dyspepsia and acid reflux are common problems faced by the adult U.S. population. These symptoms frequently necessitate an upper gastrointestinal endoscopy, which is performed to rule out anatomic diseases. Moreover, these symptoms can be associated with complications such as erosive esophagitis, Barrett's esophagus, peptic ulcer disease and gastric cancer. The role and the level of acid (pH levels) in patients presenting with these symptoms has been poorly defined in previous studies since they have used catheter based pH systems which provided recordings only for 24 hours, at only a single location in the esophagus or stomach, and has been associated with patient discomfort leading to inconsistent results. This pilot project will attempt to study the level of acid exposure in the distal esophagus and proximal stomach of patients and correlate it with their symptoms.
Many individuals in the Western world are troubled by heartburn, acid regurgitation, abdominal pain (dyspepsia), or bowel habit disturbances; up to one in two subjects in cross sectional population based studies report such symptoms. Gastro-esophageal reflux (GERD) is probably the commonest chronic disease of the population of the Western world. The reported prevalence of symptomatic GERD has ranged, on average, from 15% to 25%. Similarly, dyspepsia is a common condition in the general population; the reported prevalence range in populations is 15-40%. The majority of patients have functional (or non-ulcer) dyspepsia in that they do not have any underlying structural explanation for their symptoms, such as peptic ulcer disease or reflux esophagitis. However, given the significant morbidity and absence from work associated with the condition, the pathogenesis and treatment of patients with dyspepsia still requires further research. Studies are thus needed to determine the long term effects of these symptoms on healthcare costs but in the short run to determine the correlation of symptoms to acid levels and acid exposure.
Upper Gastrointestinal Diseases & pH Recording: Continuous esophageal pH recordings are widely used to study GERD and its treatment (5). Gastric pH recordings are less used clinically, but monitoring of gastric pH has been used for the pharmacological comparison of various anti-secretory agents. Continuous pH recordings in the esophagus and stomach are usually displayed as graphs of pH versus time or as percentage of time with pH above or below a particular value (often 4.0).
Although there is no doubt that gastric acidity is directly involved in GERD pathogenesis, relationships between gastric and esophageal acidity are not clear. Lack of focus on gastric acid may relate to the general belief that gastric acid secretion is usually normal in GERD. Distinct patterns of esophageal acidity in GERD have been previously reported. There is a clear relationship between these descriptors and the present findings of integrated esophageal acidity. Previous pH-based analyses have nicely correlated esophagitis grade with acid exposure, but gastric acidity has been somewhat neglected as the major determinant of esophageal acid exposure in GERD aside from observations that acid inhibition could diminish esophageal acid exposure. Hirschowitz reported basal and pentagastrin-stimulated gastric acid secretion in esophagitis comparable to unspecified medical conditions without esophagitis. Others, however, have reported increased basal, peak, or maximal gastric acid secretion in GERD compared to healthy subjects. In studies of gastro-esophageal reflux, the esophageal pH electrode is traditionally positioned above the proximal limit of the lower esophageal sphincter (LES). This convention was adopted early on to avoid the electrode slipping into the stomach during swallowing when the esophagus shortens by 2-3 cm. As consequence, a conventionally placed electrode will only detect acid refluxing into the distal esophagus if it reaches this point 5 cm above the LES. If acid exposure of the most distal esophagus and proximal stomach is greater than that of the conventional measuring point proximal to the LES, it could have significance clinically. This reflux in the distal esophagus and proximal stomach may explain the high incidence of metaplasia and neoplasia of the most distal esophagus that occurs in the general population.
Previous studies in patients with dyspepsia have revealed either normal levels of pH or mildly elevated levels in the stomach. The correlation between the symptoms and the acid levels has been tested only in a few previous studies. The most distal esophagus and the gastroesophageal junction is exposed to significant amounts of gastric acid, even in subjects without reflux or dyspeptic symptoms. This is of importance for not only understanding the pathophysiology of these diseases but also for treatment with acid suppressive medication. Data are lacking on the benefits of effective acid inhibition with proton pump inhibitors in dyspepsia. In two large, double blind multicenter clinical trials, BOND and OPERA , patients (n=1262) with functional dyspepsia were randomized to four weeks of treatment with omeprazole 20 mg or 10 mg once daily, or placebo. The primary efficacy variable was complete absence of symptoms. The BOND but not the OPERA trial showed a significant benefit of omeprazole over placebo. Pooling the BOND and OPERA trials, complete relief of symptoms was achieved in 38.2% of the 20 mg omeprazole group (p=0.002) and in 36.0% of the 10 mg omeprazole group (p=0.02) compared with 28.2% in the placebo group suggesting that acid suppression may play a role in the treatment of these symptoms. However, before future treatment studies are conducted, correlation of patient symptoms with levels of esophageal and gastric pH levels will be important.
Current practice for measuring esophageal and gastric pH: The current catheter based 24-hr pH system involves placement of a catheter into the esophagus and stomach via the nostril. The tip of the catheter has sensors to measure esophageal and gastric pH. The patient is then sent home (after the catheter is placed, tip coming out of one nostril) and is given a box that measures pH exposure. This is uncomfortable to the patient, leading to change in their daily activities, diet, etc. with resulting data probably not reflective of their "daily habits". Moreover, since the catheter is passed blindly into the esophagus and stomach, the exact location of pH measurement is probably not accurate.
The Bravo pH System: The Bravo pH system (FDA approved) is a novel capsule based and wireless testing system, which allows a capsule, size of a kidney bean, to be attached in the esophagus or the stomach once the endoscopy has been performed. This attachment is helped with the use of a small clip, which then detaches and is passed through the patient in the stool. Preliminary studies using this Bravo pH capsule have shown good tolerability of using this, presence of 48-hour results as well as good correlation with acid suppressive therapy in these patients. To study the level of acid exposure in the stomach and the distal esophagus in patients with upper gastrointestinal diseases and symptoms, specifically in those with dyspepsia and acid reflux using a novel pH system.
Study Design: Patients presenting to the gastroenterology endoscopy unit for upper gastrointestinal symptoms will be invited to participate in the study. The patient's symptoms will be accurately noted using standardized and validated questionnaires. All patients will undergo standard upper endoscopy. The patient demographics including age, gender, ethnicity will be noted. The findings at the time of upper endoscopy such as presence of hiatal hernia, erosive esophagitis, ulcer disease, H. pylori infection, and cancer will be recorded. After the endoscopic procedure is over, two Bravo pH capsules will be placed in the distal esophagus and the proximal stomach after the landmarks have been determined endoscopically. The patients will be provided with a single pH recorder and will be asked to return to the Gastroenterology unit lab, 24-48 hours after placement. Patients will be encouraged to continue with their routine activity including meals. They will fill out a second questionnaire at the end of the study regarding any discomfort that they may have experienced with the Bravo capsule. Data will then be recorded regarding the levels of acid exposure at the sites in the esophagus and stomach, patient demographics and comfort.
Safety Evaluation: Patients who have undergone Bravo in previous studies have reported chest discomfort, chest pain, abdominal pain, and nausea. No major complications have been reported. Thus, there is not a significant risk to the patient undergoing the procedure, except that of the standard endoscopy, for which they have already been scheduled.
|Study Design||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Probability Sample|
|Study Population||The subjects in this study were selected from veterans ages 18 and above presenting for an upper endoscopy|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Original Actual Enrollment||Same as current|
|Actual Study Completion Date||October 2009|
|Actual Primary Completion Date||October 2009 (Final data collection date for primary outcome measure)|
|Ages||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||PS0019|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Prateek Sharma, MD, Department of Veterans Affairs Medical Center|
|Study Sponsor||VA Office of Research and Development|
|Collaborators||PriCara, Unit of Ortho-McNeil, Inc.|
|PRS Account||Kansas City Veteran Affairs Medical Center|
|Verification Date||March 2011|