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

Mayo Clinic

Status and phase: Enrolling; Phase 2

Conditions: Indigestion; Diabetes Mellitus

Treatments: Drug: Placebo; Drug: Ondansetron 8mg

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03865290

18-005041

P01DK068055 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Researchers are trying to understand why people with indigestion and diabetes mellitus have gastrointestinal symptoms and in particular to understand whether symptoms are related to increased sensitivity to nutrients in the small intestine. As part of this investigation, a medication called ondansetron will also be studied to determine its effects on gastrointestinal function and associated symptoms.

Full description

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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150 participants in 6 patient groups, including a placebo group

Healthy Control Ondansetron 8 mg

Experimental group

Description:

Oral Ondansetron 8 mg administered in a single does dose during gastric emptying and duodenal infusion.

Treatment:

Drug: Ondansetron 8mg

Diabetic (DM) gastroenteropathy Ondansetron 8 mg

Experimental group

Description:

Oral Ondansetron 8 mg administered in a single does dose during gastric emptying and duodenal infusion. Oral Ondansetron 8 mg administered three times a day for weeks 3-6

Treatment:

Drug: Ondansetron 8mg

Non-ulcer dyspepsia (NUD) Ondansetron 8 mg

Experimental group

Description:

Oral Ondansetron 8 mg administered in a single does dose during gastric emptying and duodenal infusion. Oral Ondansetron 8 mg administered three times a day for weeks 3-6

Treatment:

Drug: Ondansetron 8mg

Healthy Control Placebo

Placebo Comparator group

Description:

Oral matched placebo administered in a single does dose during gastric emptying and duodenal infusion.

Treatment:

Drug: Placebo

Diabetic (DM) gastroenteropathy Placebo

Placebo Comparator group

Description:

Oral matched placebo administered in a single does dose during gastric emptying and duodenal infusion. Oral matched placebo administered three times a day for weeks 3-6

Treatment:

Drug: Placebo

Non-ulcer dyspepsia (NUD) Placebo

Placebo Comparator group

Description:

Oral matched placebo administered in a single does dose during gastric emptying and duodenal infusion. Oral matched placebo administered three times a day for weeks 3-6

Treatment:

Drug: Placebo