Aims of research project:

To identify key features of the gastro-esophageal junction (structure and function) that protects the esophagus from gastro-esophageal reflux investigated by combined high resolution manometry and magnetic resonance imaging.

Hypothesis:

1. Functional factors including GEJ function (e.g. sphincter pressure) and proximal gastric distension determine whether or not TLESR occurs; however
2. Structural factors including separation of GEJ anatomy, intra-gastric distribution of the meal and secretions determine whether TLESR is accompanied by no reflux event, gas reflux (belching) or reflux of ingested food and gastric secretion ('true reflux').
3. Initial findings by descriptive studies in healthy volunteers (study #1) and patients with mild to moderate gastro-esophageal reflux disease (study #2) will be further interrogated by a randomized, double-blind control trial of baclofen in patients with GORD; a medication that inhibits reflux by effects on GOJ function (study #3) .

Inclusion criteria:

Study #1:

• healthy male and female volunteers
• aged at least 18 and not more than 49 y
• no history of gastrointestinal symptoms
• able to communicate well with the investigators and to comply with the requirements for the entire study
• who provided written informed consent before participating in the study, after being given a full description of the trail.

Study #2 and #3:

• male and female patients with mild to moderate gastro-oesophageal reflux disease defined by presence of (1) reflux symptoms (2) pathological esophageal acid exposure between 5-10% on 24 hour ambulatory testing
• aged at least 18 and not more than 49 y
• no history of gastrointestinal symptoms
• able to communicate well with the investigators and to comply with the requirements for the entire study
• who provided written informed consent before participating in the study, after being given a full description of the trail.

Exclusion criteria:

• with present psychiatric disorders or mental impairment limiting the ability to comply with study requirements
• with use of medications influencing upper GI motility within one week of the study (i.e. beta- blocker, calcium channel blockers, nitrates, prokinetic drugs, macrolide antibiotics)
• with regular intake of medication; occasional use of analgesic e.g. aspirin, paracetamol is allowed
• with symptoms or a history of gastrointestinal disease other than gastro-esophageal reflux disease (in study #2 and #3)
• suffering from known liver, kidney, cardiovascular, neurological or pulmonary disease
• with any evidence of infectious disease
• with evidence or history of drug or alcohol abuse
• with insufficient knowledge of the German language • who, for any reason, are unable to complete the study