Obesity is an important public health problem in the United States. The investigators hypothesize that stomach injections of botulinum toxin A (BTA), delivered through an endoscope using endoscopic ultrasound (EUS), may cause delayed gastric emptying, satiation, and reduction in body weight. This protocol is designed to study the effects and safety of gastric BTA injections. Subjects are randomized to receive placebo or one of two different doses of BTA injected into the stomach during one endoscopy, performed via the mouth. Gastric emptying, satiation, symptoms, psychological dimensions of eating behavior, and caloric intake are recorded before and after injections, and subjects are seen in follow-up for 24 weeks.

Additional information regarding study interventions can be obtained by contacting study staff.

Inclusion Criteria:

• Age ≥ 18 years and ≤ 60 years
• BMI ≥ 35 kg /m²
• No history of diabetes, gastric or small bowel surgery, known gastroparesis, prior peptic ulcer, esophagitis, or gastrointestinal stricture.
• Not pregnant or nursing. Women of childbearing potential must have a negative urine pregnancy test within 48 hours prior to each gastric emptying study, and the Botox injection procedure.

Exclusion Criteria:

• Unable or unwilling to provide written informed consent
• ASA Class III or higher
• Chronic upper abdominal pain, nausea, or vomiting
• Allergy to botulinum toxin
• Delayed gastric emptying (abnormal T ½) on baseline scintigraphic gastric emptying test
• Active esophageal, gastric, or duodenal ulceration at time of diagnostic EGD
• Allergic to both penicillins AND quinolones
• Subject has taken warfarin (Coumadin) or clopidogrel (Plavix) in the week preceding EUS