Gastric Functions & Proton Pump Inhibitor( PPI) Study
Gastric Functions & Proton Pump Inhibitor( PPI) Study
Functional dyspepsia is one of the most common 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 mechanism of symptom relief is
 unclear. Most of the previous studies were performed on healthy volunteers who received only
 a very short course of PPI. The correlation between symptom and gastric emptying is lacking
 in these studies.

 Demographic data and anthropometric measurements will be obtained for baseline assessment.
 Patients are required to complete FGI Screening Questionnaire, Functional dyspepsia symptom
 questionnaire, gastroesophageal reflux disease (GERD) symptom questionnaire and irritable
 bowel syndrome (IBS) symptom questionnaire to have a thorough assessment of their GI
 symptoms. (1) Satiety test and ghrelin profile, and (2)gastric emptying test will be arranged
 as two individual visits.

 After baseline investigations, patients will be randomly assigned to either Nexium 20 mg
 daily or identical looking placebo for 8 weeks. The patients will report their individual
 dyspeptic symptoms on weekly basis using a self-administered symptom questionnaire.

 Satiety test and ghrelin profile, gastric emptying study will be repeated at the end of
 8-week treatment.

 Hypothesis: Long-term PPI relieves dyspeptic symptom through acceleration of gastric emptying
 rate.
Background

 Functional dyspepsia is one of the commonest digestive disorders. It is a functional
 gastrointestinal disorder which is characterized by chronic recurrent epigastric symptoms
 such as pain, burning and a variety of postprandial symptoms with absence of demonstrable
 organic pathology identified on investigations. It has been reported that functional
 dyspepsia affects 10-30% of adult population.

 The pathophysiology of functional dyspepsia is uncertain. It is thought to be a heterogeneous
 disorder. Various factors have been implicated in the pathophysiology of functional
 dyspepsia. It has been reported that delayed gastric emptying, impaired proximal gastric
 accommodation, visceral hypersensitivity and Helicobacter pylori gastritis play a role in
 development of functional dyspepsia. However, the correlation between these physiological
 abnormalities and symptomatology of functional dyspepsia is poor. It is still controversial
 whether these pathophysiological factors are responsible for specific symptoms in functional
 dyspepsia.

 While mechanism of functional dyspepsia is unclear, treatment has also been far from
 satisfactory. Proton pump inhibitor has been recommended as the first line treatment for
 functional dyspepsia and it has been shown that the use of PPI is associated with a 14%
 reduction in risk of persistent dyspepsia compared to placebo. However, the mechanism of
 symptom relief is unclear. While PPI exerts its effect primarily through suppression of
 acid-induced symptoms, recent studies have shown that PPI may affect gastric motility
 function such as gastric volume, gastric emptying and trigger of migratory motor complex.
 Most of these studies were performed on healthy volunteers who received only a very short
 course of PPI. The correlation between symptom and gastric emptying is lacking in these
 studies.

 Aims

 -  To evaluate the effect of esomeprazole on gastric emptying

 -  To evaluate the relationship between dyspeptic symptom and gastric emptying

 Hypothesis

 Long-term PPI relieves dyspeptic symptom through acceleration of gastric emptying rate

 Study design

 Double-blind randomized placebo-controlled trial

 Baseline assessment

 -  Demographic: age, gender

 -  Anthropometric measurements: body mass index, height, weight and waist circumference

 -  FGI Screening Questionnaire (v.2, 20090106) for screening of functional gastrointestinal
 disorder according to Rome III criteria.

 -  Functional dyspepsia symptom questionnaire (FDSQ) (20080416): an 8-item dyspeptic
 symptom score questionnaire: 4-point Likert scale for assessment of epigastric pain,
 epigastric burning, belching, bloating, postprandial fullness, early satiation, nausea
 and vomiting and a global dyspeptic symptom assessment.

 -  GERD Symptom questionnaire (GERDSQ) (20080416): GERD symptom score questionnaire.

 -  Irritable Bowel Syndrome Symptom questionnaire (IBSSQ) (20080428): IBS symptom score
 questionnaire.

 Satiety test and ghrelin profile

 After an overnight fast, the patients are instructed to ingest Ensure® (1.06 kcal/ml; 22%
 fat, 64% carbohydrate, and 14% protein) at constant rate of 30ml/min, and complete a Fullness
 Rating Scale (FRS) at 3-min intervals (ie. 0min, 3min, 6min…). The test will stop when a
 score of 4, which is equivalent to unbearable fullness, is reached in FRS. The volume
 (calorie) of Ensure that is ingested will be recorded and it serves as surrogate marker of
 satiety function. Serial blood sample (2ml each) will also be taken at 0, 30, 60, 90, 120min
 during test for assay of ghrelin and gastrin profile. If the test is stopped before 120
 minutes, the remaining blood will still be taken according to schedule.

 Gastric emptying test with FANci2

 Measurement of gastric emptying rate of solid meal will be accomplished using 13C-octanoic
 acid breath test within 7 days after satiety test. After 12-hour fasting, the patient is
 required to ingest a pan-fried egg with 2 pieces of bread that contains 100 ul of
 13C-octanoic acid dissolved in egg yolk. The exhaled gas will be collected at 15-minute
 intervals until 4 hours have passed. The 13CO2 content of the exhaled gas will be measured by
 a breath test device (FANci2, FAN GmbH.,Germany). 13CO2 is released after the 13C-octanoic
 acid enriched meal is emptied into the stomach and digested in duodenum.

 Randomization of treatment

 After baseline investigations, patients will be randomly assigned to either Esomeprazole 20
 mg 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 interval
 visits.

 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?". Satiety test and
 blood sampling, gastric emptying study will be repeated at the end of 8-week treatment.
Inclusion Criteria:

 -  Patients with functional dyspepsia that fulfill Rome III criteria attending GI clinic
 or endoscopy center

 -  Age 18-60 years old

 -  Provision of written consent

 -  Negative upper endoscopy (oesophagogastroduodenoscopy or OGD) finding

 Exclusion Criteria:

 -  Diabetes mellitis

 -  Frequent (once or more per week) acid reflux or heartburn symptoms

 -  Concurrent medications that affect GI motility

 -  Concurrent use of TCA

 -  History of gastric surgery

 -  Organic disease as cause of dyspepsia

 -  H. pylori infection

 -  Use of PPI or NSAID in the past 4 weeks

 -  Pregnancy

 -  Known hypersensitivity to PPI