A Randomized Trial of Medical and Surgical Treatments for Patients With GERD Symptoms That Are Refractory to Proton Pump Inhibitors

Exclusion Criteria

• •Patients who do not have heartburn, defined as a burning sensation in the chest
• •Patients unwilling or unable to provide informed consent
• •Pregnancy or women unwilling to use effective contraception
• •Age \<18 or \>70 years
• •History of surgery on the stomach or esophagus
• •History of seizure disorder
• •History of heart block
• •Allergy to or previous inability to tolerate study medications (omeprazole, baclofen, desipramine)
• •Esophageal varices
• •Cirrhosis
• •Co-morbidity of sufficient severity to preclude elective surgery (e.g. pulmonary, cardiac, renal, liver disease)
• •History of disorders that can cause medically-refractory "GERD symptoms" (eosinophilic esophagitis, neoplasms of the upper gastrointestinal tract, gastroparesis, achalasia)
• •Myocardial infarction within the past 6 months
• •History of schizophrenia
• •Current use of clopidogrel
• •Patients who have a contraindication to omeprazole or baclofen or who require therapy with a medication that has a clinically important drug interaction with omeprazole or baclofen.
• •Patients who, in the judgment of the PI, are not suitable candidates for therapy with a study medication (omeprazole, baclofen, desipramine)
• •Initial GERD-HRQL score: Total score \<6 and/or all heartburn scores \<2
• •Inability to tolerate omeprazole during the 2-week treatment phase (before randomization)
• •GERD-HRQL after two weeks of treatment with omeprazole: Total score less than or equal to 50% of initial GERD-HRQL score and/or all heartburn scores \<2
• •Laboratory abnormalities including:
• •* Platelet count \<100,000
• •* international normalized ratio (INR) \>1.5 (off anticoagulants)
• •* Serum creatinine \>2.0 mg per deciliter
• •Endoscopic abnormalities including:
• •* Los Angeles Classification of Oesophagitis (LA grade) C or D reflux esophagitis
• •* Active ulceration of the esophagus that is not due to reflux esophagitis
• •* Candida esophagitis
• •* Esophageal varices
• •* Active ulceration of the stomach and/or duodenum
• •* Neoplasm of the esophagus, stomach or duodenum
• •* Gastric outlet obstruction
• •* Eosinophilic esophagitis at least (15 eosinophils per high power field in any esophageal biopsy specimen)
• •Manometric abnormalities including:
• •* Achalasia
• •* Complete aperistalsis
• •Negative SAP ( 95%) for acid reflux, non-acid reflux and all reflux on baseline combined esophageal pH/MII monitoring and normal acid reflux (esophageal pH\<4 for \<4.2% of the 24-hour monitoring period)
• •Study surgeon identifies a contraindication to laparoscopic Nissen fundoplication
• •Morbid obesity (BMI at least 40)
• •Large paraesophageal hernia