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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Indigestion
• Intervention / Treatment: Drug: Ondansetron 8mg; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kelly J Feuerhak; Phone Number: 507-255-6802; Email: Feuerhak.Kelly@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Principal Investigator: Adil E Bharucha, MD
      • Contact: Kelly J Feuerhak; Phone Number: 507-255-6802; Email: Feuerhak.Kelly@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Control Ondansetron 8 mg; Oral Ondansetron 8 mg administered in a single does dose during gastric emptying and duodenal infusion.	Drug: Ondansetron 8mg; Oral Ondansetron 8 mg; Other Names: Zofran
Experimental: Diabetic (DM) gastroenteropathy Ondansetron 8 mg; 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	Drug: Ondansetron 8mg; Oral Ondansetron 8 mg; Other Names: Zofran
Experimental: Non-ulcer dyspepsia (NUD) Ondansetron 8 mg; 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	Drug: Ondansetron 8mg; Oral Ondansetron 8 mg; Other Names: Zofran
Placebo Comparator: Healthy Control Placebo; Oral matched placebo administered in a single does dose during gastric emptying and duodenal infusion.	Drug: Placebo; Oral matched placebo
Placebo Comparator: Diabetic (DM) gastroenteropathy Placebo; 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	Drug: Placebo; Oral matched placebo
Placebo Comparator: Non-ulcer dyspepsia (NUD) Placebo; 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	Drug: Placebo; Oral matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in severity of symptoms during enteral infusion	Visual analog scale (VAS) used to measure the change in symptom severity with a scale of 0=absent, 1=light, 2=moderate, 3=severe, 4=intolerable	baseline, every 15 minutes up to 8 hours
Change in severity of symptoms during gastric emptying study	Visual analog scale (VAS) used to measure the change in symptom severity with a scale of 0=absent, 1=light, 2=moderate, 3=severe, 4=intolerable	baseline, every 15 minutes up to 2 hours
Change in severity of daily symptoms	Gastroparesis Cardinal Symptom Index - Daily Diary (GCSI-DD) used to measure the change in symptoms severity with a scale of 0=none, 1= very mild, 2=mild,3=moderate, 4=severe, 5= very severe	Baseline, daily for six weeks
Change in severity of gastrointestinal symptoms	Gastrointestinal Disorders - Symptom Severity Index (PAGI-SYM) used to measure the change in symptoms severity with a scale of 0=none, 1= very mild, 2=mild,3=moderate, 4=severe, 5= very severe	Baseline, 2 weeks, 6 weeks
Change in severity of gastrointestinal symptoms effect on Quality of Life	Gastrointestinal Disorders - Quality of Life and Well-Being (PAGI-QOL) used to measure the change in symptoms severity with a scale of 0=none, 1= very mild, 2=mild,3=moderate, 4=severe, 5= very severe	Baseline, 2 weeks, 6 weeks
Change in effect of Gastrointestinal symptoms on Quality of Life	Nepean Dyspepsia Index used to measure symptoms severity with a scale of 0=none, 1= very mild, 2=mild,3=moderate, 4=severe, 5= very severe	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose level	Compare the changes in glucose level during a lipid infusion	baseline, approximately 60-120 minutes
Insulin level	Compare the changes in insulin level during a lipid infusion	baseline, approximately 60-120 minutes
C-peptide level	Compare the changes in C-peptide level during a lipid infusion	baseline, approximately 60-120 minutes
Glucagon-like Peptide 1 (GLP-1)	Compare the changes in Glucagon-like Peptide 1 (GLP-1) level during a lipid infusion	baseline, approximately 60-120 minutes
Cholecystokinin (CCK)	Compare the changes in Cholecystokinin (CCK) level during a lipid infusion	baseline, approximately 60-120 minutes
Ghrelin	Compare the changes in Ghrelin level during a lipid infusion	baseline, approximately 60-120 minutes
Peptide YY (PYY)	Compare the change in Peptide YY (PYY) level during a lipid infusion	baseline, approximately 60-120 minutes
Plasma	Compare the change in plasma level during a lipid infusion	baseline, approximately 60-120 minutes
Effect of gastrointestinal symptoms on Quality of Life - Nepean Dyspepsia index	Score is derived from 25 items pertaining to QOL	Baseline
Severity of gastrointestinal symptoms - Nepean Dyspepsia index	Nepean Dyspepsia Index is used to measure symptom severity with a scale of 0=none, 1= very mild, 2=mild,3=moderate, 4=severe, 5= very severe	Baseline

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Adil E Bharucha, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2019
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Signs and Symptoms, Digestive; Diabetes Mellitus; Dyspepsia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Ondansetron
• Other Study ID Numbers: 18-005041; P01DK068055 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes