BRAVO Study for Functional Dyspepsia (BD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Chinese University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Justin Che-Yuen Wu, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01349413
First received: May 5, 2011
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

Background:

Functional dyspepsia is one of the commonest digestive disorders. The pathophysiology of functional dyspepsia is uncertain. Proton pump inhibitor (PPI) has been recommended as the first line treatment for functional dyspepsia. However, the results on effectiveness of PPI are conflicting and it has been suggested that PPI is only effective for acid-related symptoms.

The investigators plan to use a wireless pH monitoring system positioned at the junction of esophagus and stomach to evaluate the chronological relationship between acid exposure at this region and symptoms of dyspepsia as well as its impact on the efficacy of acid suppressive therapy in treatment of functional dyspepsia.

Indication:

Functional dyspepsia patients

Study center(s):

Prince of Wales Hospital, Hong Kong

Aims:

  1. To evaluate the chronological relationship between acid exposure at squamo-columnar junction (SCJ) and dyspeptic symptom in different subtypes of functional dyspepsia
  2. To evaluate the relationship between acid exposure at squamo-columnar junction and dyspeptic symptom response to PPI
  3. To compare the efficacy of PPI and placebo in treating functional dyspepsia patients

Study medication:

Esomeprazole 20mg vs Placebo o.d.

Study design:

Double-blind randomized placebo-controlled trial

Number of subjects: 130

Patient population:

Functional dyspepsia patients without concomitant gastroesophageal reflux disease (GERD)

Duration of study:

1 June 2010 - 30 May 2012

Primary variable(s):

Proportion of patients who report positive response to adequate relief of dyspeptic symptoms at week 8

Secondary variable(s):

Dyspeptic symptom scores, symptom association probability of dyspeptic symptoms in relation to esophageal pH of less than 4 as measured at 1 cm above SCJ.

Number of visits: 2

Hypothesis:

Increased acid exposure at SCJ contributes to dyspeptic symptom and predicts treatment response to PPI in FD patients without concomitant GERD


Condition Intervention Phase
Dyspepsia
Gastroesophageal Reflux
Drug: Esomeprazole 20mg
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Role of Gastroesophageal Acid Reflux at Squamo-columnar Junction in Functional Dyspepsia

Resource links provided by NLM:


Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • The primary outcome measure is the proportion of patients who report positive response to adequate relief of dyspeptic symptoms at week 8. [ Time Frame: Week 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The secondary outcome measures include dyspeptic symptom scores, symptom association probability of dyspeptic symptoms in relation to esophageal pH of less than 4 as measured at 1 cm above SCJ. [ Time Frame: 1st visit and 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 130
Study Start Date: August 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Identical looking placebo (once daily)
Other: Placebo
Identical looking placebo
Experimental: PPI
Esomeprazole 20mg daily
Drug: Esomeprazole 20mg
Oral Esomeprazole 20mg daily for 8 weeks

  Hide Detailed Description

Detailed Description:

Baseline assessment:

All patients will be invited to complete self-administered questionnaires for demographics and baseline symptom assessment

  • Demographics: age, gender
  • Screening of functional gastrointestinal disorder based on the Rome III questionnaires
  • Functional dyspepsia symptom questionnaire: an 8-item dyspeptic symptom score questionnaire using 4-point (0-3) Likert scale based on recall of the past 7 days for assessment of epigastric pain, epigastric burning, belching, bloating, postprandial fullness, early satiation, nausea and vomiting. Functional dyspepsia will be further classified into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) according to the Rome III definitions.
  • Global dyspeptic symptom assessment: a dichotomous patient-reported scale in which they are asked to give a response of either "Yes" or "No" to the inquiry "Do you have adequate relief of dyspeptic symptom over the last 7 days?"
  • GERD symptom questionnaire: Patients will also be asked to report the frequency of heartburn or acid regurgitation over the last 3 months. Patients with frequency of reflux symptoms of more than twice per month are deemed to have concomitant GERD and they will be excluded from the study.
  • Psychological disorder: Patient Health Questionnaire (PHQ) will be used for screening of concomitant psychological disorder such as depression and generalized anxiety disorder.

Upper endoscopy and BRAVO pH capsule insertion:

Upper endoscopy will be arranged within 2 weeks of baseline assessment in order to exclude organic pathology such as peptic ulcer, esophagitis and neoplasm. The position and morphology of gastroesophageal junction is assessed during withdrawal of endoscope after deflation of stomach at end-expiratory of the patient in left lateral body position. The morphology of gastroesophageal junction will be graded according to the "flap valve" concept. In order to avoid the confounding effect of gross anatomical disruption of gastroesophageal junction on acid exposure at SCJ, patients with grade IV disruption of gastroesophageal junction, which refers to patulous hiatus with axial displacement of SCJ, will be excluded.

After completion of endoscopy examination, the BRAVO delivery system will be passed orally into esophagus in the same body position. The endoscope is then reintroduced to facilitate positioning of the delivery system under direct visualization. The BRAVO pH capsule will be placed at 1 cm proximal to SCJ for monitoring of acid exposure at SCJ.

Recording of esophageal pH profile and symptoms:

The wireless esophageal pH monitoring will last for 48 hours. During the study period, the patients will be instructed to engage in their usual daily activities. The patients will be given a diary documenting meals, sleeping and dyspeptic symptoms. The patient has to return the Bravo data recorder after 48 hours.

Randomization of treatment:

After completion of BRAVO pH monitoring, patients will be randomly assigned to either esomeprazole 20mg daily or identical looking placebo for 8 weeks. The random allocation sequence will be obtained from a computer-generated list of random numbers in blocks of 10. Concealed allocation is achieved by an independent staff who assigns treatments according to consecutive numbers in sealed envelopes. Study medications are dispensed as sealed packages in consecutive numbers. Medication adherence is measured by pill counts during final visit (V2).

Follow-up assessment:

The patients will report their individual dyspeptic symptoms on weekly basis using a self administered symptom questionnaire. At week 4 and week 8, they will need to give an additional rating on their overall symptom response using global symptom assessment. The patients are required to give a dichotomous response of either "yes" or "no" to the question stating "Do you have adequate relief of symptoms over the past 7 days?"

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with functional dyspepsia that fulfill Rome III criteria with inadequate relief of dyspeptic symptoms
  • Age >18
  • Provision of written consent

Exclusion Criteria:

  • Presence of organic pathology identified by upper endoscopy or other investigations
  • Presence of sliding hiatus hernia as defined by flap valve grade IV disruption of morphology at gastro-esophageal junction
  • Concurrent medications that affect gastrointestinal motility
  • Presence of acid reflux or heartburn symptoms of more than twice a month
  • History of gastric surgery
  • H. pylori infection
  • Use of PPI or NSAID in the past 4 weeks
  • Pregnancy
  • Known hypersensitivity to PPI
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01349413

Contacts
Contact: Justin C.Y. Wu, MBChB(CUHK) (852)26323476 justinwu@cuhk.edu.hk
Contact: Yawen Chan, M Phil (852)26323476 yawenchan@cuhk.edu.hk

Locations
Hong Kong
Prince of Wales Hospital Recruiting
Hong Kong, Hong Kong
Contact: Justin C.Y. Wu, MBChB(CUHK)    (852)26323476    justinwu@cuhk.edu.hk   
Principal Investigator: Justin C.Y. Wu, MBChB(CUHK)         
Sponsors and Collaborators
Chinese University of Hong Kong
  More Information

Additional Information:
No publications provided

Responsible Party: Justin Che-Yuen Wu, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT01349413     History of Changes
Other Study ID Numbers: BD
Study First Received: May 5, 2011
Last Updated: July 22, 2014
Health Authority: Hong Kong: Department of Health
Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee

Keywords provided by Chinese University of Hong Kong:
Functional dyspepsia
symptom response
postprandial fullness
gastroesophageal reflux disease
acid suppression

Additional relevant MeSH terms:
Gastroesophageal Reflux
Dyspepsia
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Esomeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014