Effects of Ondansetron on Gastrointestinal Sensorimotor Dysfunctions in Diabetes Mellitus and Dyspepsia

The primary objectives of this study are to evaluate the effects of ondansetron, on symptoms
(i) during a gastric emptying study, (ii) during enteral lipid infusion and (iii) in daily
life.

Inclusion Criteria:

- Healthy male or non-pregnant, non-breastfeeding female volunteers;

- 18-75 years old;

- Able to provide written informed consent before participating in the study

- Able to communicate adequately with the investigator and to comply with the
requirements for the entire study; including the willingness and ability to consume
the components of the test meals

- Symptoms of dyspepsia (i.e., early satiety, postprandial discomfort, nausea, vomiting,
regurgitation)

- Patients in the DM group will also require Type 1 or 2 DM of ≥ 3 years duration; in
patients with type 2 DM, the dyspepsia symptoms should have begun or worsened after DM
was diagnosed

Exclusion Criteria:

- Major abdominal surgery (i.e., appendectomy, cholecystectomy, tubal ligation,
hysterectomy, herniorrhaphy, and limited colonic resection are permissible)

- Clinical evidence (including physical exam and EKG) of significant cardiovascular,
respiratory, renal, hepatic, gastrointestinal, hematological, neurological,
psychiatric or other disease that may interfere with the objectives of the study
and/or pose safety concerns

- Current use of opiates, alpha adrenergic agonists, metoclopramide, monoamine oxidase
inhibitors, more than one serotonergic medication, and high doses of anticholinergic
agents (eg, amitriptyline greater than 50 mg daily). If medically safe, these drugs
may be discontinued for four half lives prior to study assessments.

- Treatment with GLP-1 agonists and amlyin which cause vagal blockade and may affect
central processing of pain

- Bleeding or clotting disorders or medications that increase risk of bleeding from
mucosal biopsies

- Positive tissue transglutaminase antibodies (TTG),

- Pregnant or breast-feeding females

- Known intolerance or allergy to eggs

- Poor peripheral venous access, if central venous access is not available

- Any other condition or prior therapy that, in the opinion of the investigator, would
make the patient unsuitable for the study

- History of Long QT Syndrome or prolonged QT interval (i.e., corrected QT interval >
480 ms)

- Current symptoms of a functional gastrointestinal disorder assessed by questionnaire

- Severe vomiting that would preclude tube placement or participation in the study

- Structural cause for symptoms by endoscopy within the past 12 months

- Patients with gastric pacemakers