Esomeprazole and Gastric Emptying of Beer
Condition: Gastroesophageal Reflux; Heartburn
MeSH terms: Gastroesophageal Reflux; Heartburn
Study type: Interventional
Phase: Phase 4

Summary: 
      To investigate the effect of 20 mg esomeprazole daily for one week on gastric emptying of 500
      ml beer, the consecutive blood alcohol levels, the gastroesophageal reflux and plasma levels
      of gastrin and CCK in a randomized, placebo-controlled, double-blinded manner in 16 healthy
      male volunteers.

      Hypothesis:

      The combined taking of esomeprazole and beer will inhibit gastric emptying as compared to the
      intake of beer alone. This will induce a delay of the ethanol absorption and of the
      consecutive blood ethanol concentrations. Gastric acid secretion after beer will be reduced
      after esomeprazole treatment. Therefore, gastroesophageal acid reflux will be reduced after
      the combined taking. We speculate that gastrin, but not CCK plasma levels, will be increased
      after the combined taking as compared to beer alone. Both, beer and PPIs, have stimulatory
      effects on gastrin release. However, the secretion of CCK from duodenal CCK-cells is
      inhibited when gastric emptying is prolonged.
    

Detailed description: 
      Sixteen healthy, male and non-smoking volunteers will be enrolled in this study. The subjects
      will be treated with placebo or with 20 mg esomeprazole daily for one week before gastric
      emptying will be determined. The sequence of the tests (verum or placebo) will be randomised
      in a cross over design. In each subject at most one test will be performed every 2 weeks to
      ensure one week without treatment (wash-out-phase) between both experiments.

      All examinations will be performed in the afternoon. After a small breakfast in the morning
      subjects fast for at least 8 hours. During the examination, all subjects are sitting slightly
      leaned backwards. A double lumen nasogastric tube (Ch 14, Laboratories Pharmaceutiques Vygon,
      Ecouen, France) will be positioned in the most dependent part of the stomach and a pH-probe
      (F8/IR blue line, SME Medizintechnik, Weil am Rhein) will be positioned 5 cm above the lower
      esophageal sphincter. 500 ml beer will then be instilled into the stomach over 5 min. Gastric
      emptying will be determined every 10 min for 2 hours by ultrasonography.

      Withdrawal criteria The trial can be stopped anytime by the volunteer without specified
      reasons or by the investigator in case of incompliance of the volunteer or subsequent
      incidence of exclusion criteria. In case of hypersensitive or allergic reaction against the
      medication or side effects of the medication, such as urtication, angioneurotic edema,
      vomiting, cardiovascular reaction (systolic blood pressure under 100 mm/Hg), paraesthesia,
      confusion, bronchial spasm or fever, the study will also be stopped.

      In case of withdrawal of volunteers, up to four additional volunteers can be recruited to
      complete totalling 16 volunteers.

      Assessment of safety Esomeprazole is a frequently administered drug in the therapy of
      particularly gastroesophageal reflux disease, gastritis and gastric or duodenal ulcers. Side
      effects are very rare, headache, abdominal pain, diarrhoea, bloating, nausea, vomiting and
      constipation are thereof the most frequent. The methods used in this study are clinical
      routine procedures and imply -if used by skilful physicians as in this study - no risk for
      complications.

      To detect side effects or complications the investigator is present in the examination room
      during the whole study and blood pressure and heart rate are measured every 15 minutes.
      Before the each study and during the introduction procedure a physical examination will be
      performed by the investigator.

      Ultrasonography Ultrasonography of the antrum and the fundus represents a highly reliable and
      reproducible radiation-avoiding method for determination of gastric emptying [11-14]. To
      determine gastric emptying of the proximal and distal stomach, we will use a curved array
      scanner with a 3.25 MHz ultrasound transducer (Sonoline Sienna®; Siemens, Germany). We
      determine emptying of the distal stomach by measuring the cross-sectional area of the antrum
      at the level of the superior mesenteric vein and the aorta [12, 13]. The vessels are used to
      standardize the position of the scans. This antral area is scanned before, immediately after
      intragastrical application of the test solution and every 10 minutes for two hours.

      Gastic emptying of the proximal stomach will be measured immediately after the application
      and every 10 min until the fundus is emptied completely using the following ultrasonographic
      method: the transducer will be positioned in the epigastrium at the left subcostal margin and
      tilted cranially. The maximal angle of view of the scanner is used to visualize as much of
      the proximal stomach as possible. Two standardized sonographic image sections are chosen:
      First, a sagital section with the left renal pelvis in a longitudinal projection, the left
      lobe of the liver and the tail of the pancreas as internal landmarks. The transducer is then
      rotated 90° clockwise to obtain an oblique frontal section where the left hemidiaphragm, the
      top margin of the fundus, and the liver parenchyma serve as landmarks. A proximal gastric
      area is outlined in the sagital section by tracing from the top margin of the fundus and 7 cm
      downward along the axis of the stomach. The maximal diameter in the oblique frontal section,
      kept within 7 cm along the axis of the proximal stomach, is chosen as the second measure.
      Both measurements are combined to estimate an approximate volume of the fundus [11].

      The inner echogenic layer corresponding to the interface between the gastric content and the
      mucosa of the gastric wall is outlined. The measurements were repeated twice and the mean
      value is used. The areas of the antrum and the fundus and the diameter of the fundus are
      traced by the internal calliper provided with the ultrasound instrument. All ultrasonographic
      parameters will be measured twice, the mean of both measurements will be chosen to be
      representative.

      Gastric half emptying time (t(1/2)) will determined separately for the fundus and the antrum.

      Plasma gastrin, plasma CCK and serum ethanol concentrations Blood samples (10 ml) will be
      drawn at baseline and every 15 min after application of the test solution for 2 hours for the
      determination of serum ethanol concentrations. Samples will be centrifuged immediately at 4°
      C. The serum concentration of ethanol will be determined using the alcohol-dehydrogenase
      method (Ethylalkohol, Roche Diagnostics GmbH, Mannheim, Germany). The plasma concentrations
      of gastrin will be measured by the Institute for Clinical Chemistry at the University
      Hospital Mannheim by radioimmunassays (RIA) and that of CCK at the Universityhospital Basel
      (Professor Ch. Beglinger, no round robin test certificate available).

      Gastroesophageal reflux The intraesophageal pH (5 cm above the lower esophageal sphincter)
      will be recorded for 4 hours by GastroScan II (SME Medizintechnik, Sprendlingen). The correct
      position of the tip of the pH-probe will be measured by pH-metry during the visit for the
      screening examinations. The portion of intraesophageal pH<4 and the DeMeester-Score
      (frequency and duration of pH<4) will be calculated.

      Gastrointestinal complaints The volunteers mark additionally on a visual analogue scale (VAS
      0-100) their intensity of fullness, bloating, heartburn and satiety before the ingestion of
      beer and than in 10 min intervals for 2 hours.

      Statistical analysis Statistical significances for differences between gastric emptying
      rates, blood alcohol concentrations and gastroesophageal reflux will be determined using
      student´s t-test.
    

Intervention name(s): esomeprazole 20 mg
Intervention type(s): Drug
Intervention MeSH terms: Esomeprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: esomeprazole, gastric emptying, reflux